Breast Cancer

Many primary care physicians – and even some oncologists – are unaware of common long-term side effects of four widely used breast and colorectal cancer drugs, a national survey by the National Cancer Institute reveals.

Only 6% of primary care physicians were able to identify the main long-term effects (LEs) of doxorubicin (Adriamycin), paclitaxel (Taxol), oxaliplatin (Eloxatin), and cyclophosphamide (Cytoxan), compared with 65% of oncologists surveyed.

The results are not surprising, but they underscore the need for ongoing education among all physicians who care for the more than 12 million cancer survivors in the United States, lead author Dr. Larissa Nekhlyudov said during a press briefing highlighting research to be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO).

"These findings emphasize that in the transition of patients from oncology to primary care settings, primary care providers should be informed about the late effects of cancer treatment so that they may be better prepared to recognize and address these among cancer survivors in their care," said Dr. Nekhlyudov, a primary care physician (PCP) with Harvard Medical School in Boston and Harvard Vanguard Medical Associates in Kenmore, Mass. "Whether this will be achieved with survivorship care plans needs to be evaluated."

The "Survey of Physician Attitudes Regarding the Care of Cancer Survivors" was launched by the National Cancer Institute in 2009, with one survey mailed to a nationally representative sample of 1,072 PCPs and the other to 1,130 medical oncologists who only cared for patients with colorectal or breast cancer.

When asked to report the five LEs they had observed and/or had seen reported in the literature for each of the four standard chemotherapy drugs, 95% of oncologists identified cardiac dysfunction as an LE of doxorubicin, compared with 55% of PCPs (P less than .0001), Dr. Nekhlyudov said.

Similarly, peripheral neuropathy was correctly identified as an LE of paclitaxel and of oxaliplatin by 97% of oncologists, but by only 27% and 22%, respectively, of PCPs (both P less than .0001).

The survey suggests, however, that some oncologists could also use additional continuing education. Premature menopause and secondary malignancies – two long-term effects associated with the alkylating agent cyclophosphamide – were identified by only 71% and 62% of oncologists, respectively, along with 15% and 17%, respectively, of PCPs.

Oncologists and PCPs mostly missed pulmonary fibrosis as a late effect for paclitaxel (5% and 6%, respectively; P = .42) or oxaliplatin (5% and. 9%, respectively; P = .0002). They did a little better in pointing out a possible association with cyclophosphamide (20.6% and 13%; P less than .0001), which has been noted in the literature, she observed.

Dr. Nekhlyudov suggested that the lack of awareness among oncologists is likely because much of the focus has been on the treatment of cancer, and only recently have physicians become aware of the importance of survivorship and the potential for late effects.

"While it is surprising that oncologists were not more aware of late effects, I think that as more and more attention is placed on cancer survivorship, oncologists will become more equipped with that information," she said.

ASCO president and press briefing comoderator Dr. Michael Link said the problem of survivorship has long been recognized in pediatric oncology, where patients frequently relocate, outgrow their pediatrician, or even deny they ever had cancer. Groups such as ASCO and the Institute of Medicine, most recently through its "Lost in Transition" report, have offered guidance for improving transitions among survivors, including the provision of a cancer care plan.

"I think the need for all of this has been highlighted in this abstract and certainly, it’s a shot across the bow with things that need to be done," he said.

In adjusted analyses, oncologists who were not board certified were less likely to identify the main LEs for all four drugs (odds ratio, 0.58).Oncologists were more likely to know their LEs if they spent 51%-90% of their time on patient care (OR, 1.87) or more than 90% of their time with patients (OR, 1.82). Age, sex, race, U.S. training, type of practice, and percentage of uninsured patients were not associated with LE awareness, Dr. Nekhlyudov said.

Previous results from the survey reported at last year’s ASCO annual meeting indicated that PCPs had low confidence in their knowledge of breast and colon cancer survivors, and reported low marks for their skills in caring for these patients. In addition, neither PCPs nor oncologists felt that a PCP-led model was ideal for survivorship care (J. Clin. Oncol. 2011;29[suppl.];abstract CRA9006).

Dr. Nekhlyudov will formally present her study at ASCO at 5:30 p.m. June 2. The abstract can be viewed at www.abstract.asco.org.

The authors reported no disclosures.

Many primary care physicians – and even some oncologists – are unaware of common long-term side effects of four widely used breast and colorectal cancer drugs, a national survey by the National Cancer Institute reveals.

Only 6% of primary care physicians were able to identify the main long-term effects (LEs) of doxorubicin (Adriamycin), paclitaxel (Taxol), oxaliplatin (Eloxatin), and cyclophosphamide (Cytoxan), compared with 65% of oncologists surveyed.

The results are not surprising, but they underscore the need for ongoing education among all physicians who care for the more than 12 million cancer survivors in the United States, lead author Dr. Larissa Nekhlyudov said during a press briefing highlighting research to be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO).

"These findings emphasize that in the transition of patients from oncology to primary care settings, primary care providers should be informed about the late effects of cancer treatment so that they may be better prepared to recognize and address these among cancer survivors in their care," said Dr. Nekhlyudov, a primary care physician (PCP) with Harvard Medical School in Boston and Harvard Vanguard Medical Associates in Kenmore, Mass. "Whether this will be achieved with survivorship care plans needs to be evaluated."

The "Survey of Physician Attitudes Regarding the Care of Cancer Survivors" was launched by the National Cancer Institute in 2009, with one survey mailed to a nationally representative sample of 1,072 PCPs and the other to 1,130 medical oncologists who only cared for patients with colorectal or breast cancer.

When asked to report the five LEs they had observed and/or had seen reported in the literature for each of the four standard chemotherapy drugs, 95% of oncologists identified cardiac dysfunction as an LE of doxorubicin, compared with 55% of PCPs (P less than .0001), Dr. Nekhlyudov said.

Similarly, peripheral neuropathy was correctly identified as an LE of paclitaxel and of oxaliplatin by 97% of oncologists, but by only 27% and 22%, respectively, of PCPs (both P less than .0001).

The survey suggests, however, that some oncologists could also use additional continuing education. Premature menopause and secondary malignancies – two long-term effects associated with the alkylating agent cyclophosphamide – were identified by only 71% and 62% of oncologists, respectively, along with 15% and 17%, respectively, of PCPs.

Oncologists and PCPs mostly missed pulmonary fibrosis as a late effect for paclitaxel (5% and 6%, respectively; P = .42) or oxaliplatin (5% and. 9%, respectively; P = .0002). They did a little better in pointing out a possible association with cyclophosphamide (20.6% and 13%; P less than .0001), which has been noted in the literature, she observed.

Dr. Nekhlyudov suggested that the lack of awareness among oncologists is likely because much of the focus has been on the treatment of cancer, and only recently have physicians become aware of the importance of survivorship and the potential for late effects.

"While it is surprising that oncologists were not more aware of late effects, I think that as more and more attention is placed on cancer survivorship, oncologists will become more equipped with that information," she said.

ASCO president and press briefing comoderator Dr. Michael Link said the problem of survivorship has long been recognized in pediatric oncology, where patients frequently relocate, outgrow their pediatrician, or even deny they ever had cancer. Groups such as ASCO and the Institute of Medicine, most recently through its "Lost in Transition" report, have offered guidance for improving transitions among survivors, including the provision of a cancer care plan.

"I think the need for all of this has been highlighted in this abstract and certainly, it’s a shot across the bow with things that need to be done," he said.

In adjusted analyses, oncologists who were not board certified were less likely to identify the main LEs for all four drugs (odds ratio, 0.58).Oncologists were more likely to know their LEs if they spent 51%-90% of their time on patient care (OR, 1.87) or more than 90% of their time with patients (OR, 1.82). Age, sex, race, U.S. training, type of practice, and percentage of uninsured patients were not associated with LE awareness, Dr. Nekhlyudov said.

Previous results from the survey reported at last year’s ASCO annual meeting indicated that PCPs had low confidence in their knowledge of breast and colon cancer survivors, and reported low marks for their skills in caring for these patients. In addition, neither PCPs nor oncologists felt that a PCP-led model was ideal for survivorship care (J. Clin. Oncol. 2011;29[suppl.];abstract CRA9006).

Dr. Nekhlyudov will formally present her study at ASCO at 5:30 p.m. June 2. The abstract can be viewed at www.abstract.asco.org.

The authors reported no disclosures.

Many primary care physicians – and even some oncologists – are unaware of common long-term side effects of four widely used breast and colorectal cancer drugs, a national survey by the National Cancer Institute reveals.

Only 6% of primary care physicians were able to identify the main long-term effects (LEs) of doxorubicin (Adriamycin), paclitaxel (Taxol), oxaliplatin (Eloxatin), and cyclophosphamide (Cytoxan), compared with 65% of oncologists surveyed.

The results are not surprising, but they underscore the need for ongoing education among all physicians who care for the more than 12 million cancer survivors in the United States, lead author Dr. Larissa Nekhlyudov said during a press briefing highlighting research to be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO).

"These findings emphasize that in the transition of patients from oncology to primary care settings, primary care providers should be informed about the late effects of cancer treatment so that they may be better prepared to recognize and address these among cancer survivors in their care," said Dr. Nekhlyudov, a primary care physician (PCP) with Harvard Medical School in Boston and Harvard Vanguard Medical Associates in Kenmore, Mass. "Whether this will be achieved with survivorship care plans needs to be evaluated."

The "Survey of Physician Attitudes Regarding the Care of Cancer Survivors" was launched by the National Cancer Institute in 2009, with one survey mailed to a nationally representative sample of 1,072 PCPs and the other to 1,130 medical oncologists who only cared for patients with colorectal or breast cancer.

When asked to report the five LEs they had observed and/or had seen reported in the literature for each of the four standard chemotherapy drugs, 95% of oncologists identified cardiac dysfunction as an LE of doxorubicin, compared with 55% of PCPs (P less than .0001), Dr. Nekhlyudov said.

Similarly, peripheral neuropathy was correctly identified as an LE of paclitaxel and of oxaliplatin by 97% of oncologists, but by only 27% and 22%, respectively, of PCPs (both P less than .0001).

The survey suggests, however, that some oncologists could also use additional continuing education. Premature menopause and secondary malignancies – two long-term effects associated with the alkylating agent cyclophosphamide – were identified by only 71% and 62% of oncologists, respectively, along with 15% and 17%, respectively, of PCPs.

Oncologists and PCPs mostly missed pulmonary fibrosis as a late effect for paclitaxel (5% and 6%, respectively; P = .42) or oxaliplatin (5% and. 9%, respectively; P = .0002). They did a little better in pointing out a possible association with cyclophosphamide (20.6% and 13%; P less than .0001), which has been noted in the literature, she observed.

Dr. Nekhlyudov suggested that the lack of awareness among oncologists is likely because much of the focus has been on the treatment of cancer, and only recently have physicians become aware of the importance of survivorship and the potential for late effects.

"While it is surprising that oncologists were not more aware of late effects, I think that as more and more attention is placed on cancer survivorship, oncologists will become more equipped with that information," she said.

ASCO president and press briefing comoderator Dr. Michael Link said the problem of survivorship has long been recognized in pediatric oncology, where patients frequently relocate, outgrow their pediatrician, or even deny they ever had cancer. Groups such as ASCO and the Institute of Medicine, most recently through its "Lost in Transition" report, have offered guidance for improving transitions among survivors, including the provision of a cancer care plan.

"I think the need for all of this has been highlighted in this abstract and certainly, it’s a shot across the bow with things that need to be done," he said.

In adjusted analyses, oncologists who were not board certified were less likely to identify the main LEs for all four drugs (odds ratio, 0.58).Oncologists were more likely to know their LEs if they spent 51%-90% of their time on patient care (OR, 1.87) or more than 90% of their time with patients (OR, 1.82). Age, sex, race, U.S. training, type of practice, and percentage of uninsured patients were not associated with LE awareness, Dr. Nekhlyudov said.

Previous results from the survey reported at last year’s ASCO annual meeting indicated that PCPs had low confidence in their knowledge of breast and colon cancer survivors, and reported low marks for their skills in caring for these patients. In addition, neither PCPs nor oncologists felt that a PCP-led model was ideal for survivorship care (J. Clin. Oncol. 2011;29[suppl.];abstract CRA9006).

Dr. Nekhlyudov will formally present her study at ASCO at 5:30 p.m. June 2. The abstract can be viewed at www.abstract.asco.org.

The authors reported no disclosures.

We have long considered completion axillary node dissection for patients with evidence of nodal metastases – and radiation following breast conserving surgery – as truths that are necessary and critical components of treatment planning for early-stage breast cancer. These treatments are not without impact, however, both in short- and long-term toxicity, as well as cost. As we begin to understand the biology that drives breast cancer growth, it has also become clear that not all treatments considered to be "standard" have a positive benefit-to-risk ratio.

A number of recently presented trials challenge the status quo, and teach us that less may indeed be sometimes better. For women who have evidence of cancer in one to two sentinel lymph nodes, and who have had breast-conserving surgery (therefore requiring radiation that includes the low axilla), the recent update to the National Comprehensive Cancer Network (NCCN) guidelines reflects these data demonstrating lack of additional benefit and increased toxicity from completion axillary dissection.

These new guidelines spare women from an increased risk of lymphedema and neuropathy, as well as delayed recovery and procedure-related pain. However, it is important to keep in mind that the inclusion criteria for these trials required breast-conserving surgery, therefore ensuring that radiation would be recommended postoperatively. For patients with more extensive disease in the axillary nodes, a full dissection is still considered the standard of care.

What should be recommended for women who have had a mastectomy and therefore do not require radiation? This is a more difficult question, as the risk of locoregional recurrence for women with a positive sentinel node who forgo radiation is unknown. For an individual patient, local radiation could be considered in the setting of minimal or limited node involvement to avoid more extensive surgery, although data for this approach are lacking.

For older patients with slow-growing, hormone-responsive, early-stage breast cancer, the risk of local recurrence is low, and the overall risk of recurrence is protracted, extending out to at least 15 years. When surgical margins are clearly negative for tumor, the question for these women is whether or not postoperative radiation is worth the time, expense, and toxicity for the expected benefit. Previous randomized data support omitting radiation for low-risk disease in women over the age of 70 who are also receiving adjuvant hormone therapy.

The data presented by Dr. Fei-Fei Liu and colleagues at the annual meeting of the American Association of Cancer Research (AACR) is the next step in identifying the biology of tumors for which radiation provides little benefit. In this series, women taking tamoxifen and whose tumors were hormone receptor–positive, did not express HER2/neu, and had low rates of proliferation as measured by Ki67, were found to have similar recurrence rates in a randomized prospective trial regardless of the use of adjuvant radiation.

This was particularly true for women over the age of 60, although there were only 103 patients in this analysis. Additional data are needed in a larger cohort with external validation of markers before this approach is incorporated into treatment guidelines. However, it is clear that a subset of women with a subset of breast cancers is unlikely to derive significant benefit from adjuvant radiation therapy for early-stage, low-proliferative, hormone receptor–positive breast cancer.

We are making progress, not only in identifying new therapies, but in learning how to more appropriately use the therapies we already have. Less is indeed sometimes better.

Dr. Rugo, associate editor of The Oncology Report, is Director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center.

We have long considered completion axillary node dissection for patients with evidence of nodal metastases – and radiation following breast conserving surgery – as truths that are necessary and critical components of treatment planning for early-stage breast cancer. These treatments are not without impact, however, both in short- and long-term toxicity, as well as cost. As we begin to understand the biology that drives breast cancer growth, it has also become clear that not all treatments considered to be "standard" have a positive benefit-to-risk ratio.

A number of recently presented trials challenge the status quo, and teach us that less may indeed be sometimes better. For women who have evidence of cancer in one to two sentinel lymph nodes, and who have had breast-conserving surgery (therefore requiring radiation that includes the low axilla), the recent update to the National Comprehensive Cancer Network (NCCN) guidelines reflects these data demonstrating lack of additional benefit and increased toxicity from completion axillary dissection.

These new guidelines spare women from an increased risk of lymphedema and neuropathy, as well as delayed recovery and procedure-related pain. However, it is important to keep in mind that the inclusion criteria for these trials required breast-conserving surgery, therefore ensuring that radiation would be recommended postoperatively. For patients with more extensive disease in the axillary nodes, a full dissection is still considered the standard of care.

What should be recommended for women who have had a mastectomy and therefore do not require radiation? This is a more difficult question, as the risk of locoregional recurrence for women with a positive sentinel node who forgo radiation is unknown. For an individual patient, local radiation could be considered in the setting of minimal or limited node involvement to avoid more extensive surgery, although data for this approach are lacking.

For older patients with slow-growing, hormone-responsive, early-stage breast cancer, the risk of local recurrence is low, and the overall risk of recurrence is protracted, extending out to at least 15 years. When surgical margins are clearly negative for tumor, the question for these women is whether or not postoperative radiation is worth the time, expense, and toxicity for the expected benefit. Previous randomized data support omitting radiation for low-risk disease in women over the age of 70 who are also receiving adjuvant hormone therapy.

The data presented by Dr. Fei-Fei Liu and colleagues at the annual meeting of the American Association of Cancer Research (AACR) is the next step in identifying the biology of tumors for which radiation provides little benefit. In this series, women taking tamoxifen and whose tumors were hormone receptor–positive, did not express HER2/neu, and had low rates of proliferation as measured by Ki67, were found to have similar recurrence rates in a randomized prospective trial regardless of the use of adjuvant radiation.

This was particularly true for women over the age of 60, although there were only 103 patients in this analysis. Additional data are needed in a larger cohort with external validation of markers before this approach is incorporated into treatment guidelines. However, it is clear that a subset of women with a subset of breast cancers is unlikely to derive significant benefit from adjuvant radiation therapy for early-stage, low-proliferative, hormone receptor–positive breast cancer.

We are making progress, not only in identifying new therapies, but in learning how to more appropriately use the therapies we already have. Less is indeed sometimes better.

Dr. Rugo, associate editor of The Oncology Report, is Director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center.

We have long considered completion axillary node dissection for patients with evidence of nodal metastases – and radiation following breast conserving surgery – as truths that are necessary and critical components of treatment planning for early-stage breast cancer. These treatments are not without impact, however, both in short- and long-term toxicity, as well as cost. As we begin to understand the biology that drives breast cancer growth, it has also become clear that not all treatments considered to be "standard" have a positive benefit-to-risk ratio.

A number of recently presented trials challenge the status quo, and teach us that less may indeed be sometimes better. For women who have evidence of cancer in one to two sentinel lymph nodes, and who have had breast-conserving surgery (therefore requiring radiation that includes the low axilla), the recent update to the National Comprehensive Cancer Network (NCCN) guidelines reflects these data demonstrating lack of additional benefit and increased toxicity from completion axillary dissection.

These new guidelines spare women from an increased risk of lymphedema and neuropathy, as well as delayed recovery and procedure-related pain. However, it is important to keep in mind that the inclusion criteria for these trials required breast-conserving surgery, therefore ensuring that radiation would be recommended postoperatively. For patients with more extensive disease in the axillary nodes, a full dissection is still considered the standard of care.

What should be recommended for women who have had a mastectomy and therefore do not require radiation? This is a more difficult question, as the risk of locoregional recurrence for women with a positive sentinel node who forgo radiation is unknown. For an individual patient, local radiation could be considered in the setting of minimal or limited node involvement to avoid more extensive surgery, although data for this approach are lacking.

For older patients with slow-growing, hormone-responsive, early-stage breast cancer, the risk of local recurrence is low, and the overall risk of recurrence is protracted, extending out to at least 15 years. When surgical margins are clearly negative for tumor, the question for these women is whether or not postoperative radiation is worth the time, expense, and toxicity for the expected benefit. Previous randomized data support omitting radiation for low-risk disease in women over the age of 70 who are also receiving adjuvant hormone therapy.

The data presented by Dr. Fei-Fei Liu and colleagues at the annual meeting of the American Association of Cancer Research (AACR) is the next step in identifying the biology of tumors for which radiation provides little benefit. In this series, women taking tamoxifen and whose tumors were hormone receptor–positive, did not express HER2/neu, and had low rates of proliferation as measured by Ki67, were found to have similar recurrence rates in a randomized prospective trial regardless of the use of adjuvant radiation.

This was particularly true for women over the age of 60, although there were only 103 patients in this analysis. Additional data are needed in a larger cohort with external validation of markers before this approach is incorporated into treatment guidelines. However, it is clear that a subset of women with a subset of breast cancers is unlikely to derive significant benefit from adjuvant radiation therapy for early-stage, low-proliferative, hormone receptor–positive breast cancer.

We are making progress, not only in identifying new therapies, but in learning how to more appropriately use the therapies we already have. Less is indeed sometimes better.

Dr. Rugo, associate editor of The Oncology Report, is Director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center.

Accelerated partial breast radiation with MammoSite balloon brachytherapy appears to control the tumor bed more effectively than whole breast irradiation, investigators reported at the annual meeting of the American Society of Breast Surgeons.

Dr. Peter Beitsch and his colleagues compared data from the society’s MammoSite Registry with prior findings from studies of whole-breast irradiation (WBI). They said the proportion of recurrences occurring in the tumor bed was much smaller with accelerated partial breast radiation (APBI) – 28% vs. about 69% in the earlier WBI data.

"While it made common sense to a lot of us that APBI should offer better rates of local control, compared to WBI, since the radiation therapy with APBI is delivered directly to the tumor site, this is the first study to have actually proven this hypothesis," Dr. Beitsch, director of the Dallas Breast Center, said in an interview.

"WBI has been held as the ‘gold standard’ for post-lumpectomy radiation therapy, and our data may change that line of thought," he added.

Randomized trials demonstrate that lumpectomy with WBI yields survival rates equivalent to those seen with mastectomy; they also show that WBI has no impact on the ipsilateral occurrence of new "elsewhere" cancers in quadrants away from the primary tumor quadrant. Dr. Beitsch explained during a press briefing.

In all such trials, thus far, tumor bed recurrence rates have been higher than were the rates of ipsilateral "elsewhere" cancers, he said.

Now, however, 5-year actuarial data from 1,449 cases in 1,440 patients in the MammoSite registry show the opposite. The patients were treated at 97 institutions between May 2002 and July 2004. Most patients, 87%, were diagnosed with invasive breast cancer and the rest, 13%, with ductal carcinoma in situ (DCIS). Median follow up was 60 months.

Dr. Beitsch reported there have been 50 (3.5%) ipsilateral breast tumor recurrences: 14 (1.0%) at the initial tumor site and 36 (2.5%) elsewhere in the breast. The total actuarial rate of ipsilateral breast tumor recurrence was 3.61% (3.65 % for invasive disease and 3.36 % for DCIS). Tumor bed recurrences accounted for 28% of all recurrences, whereas recurrences elsewhere added up to 72%.

In contrast, historical data on whole-breast irradiation (WBI) from six studies demonstrate that tumor bed recurrences are about twice as common as recurrences elsewhere, approximately 69% vs. about 31% elsewhere, said Dr. Beitsch, co-principal investigator for the registry and lead author on the study.

The new findings contrast with a controversial retrospective study of breast brachytherapy in nearly 93,000 older women with invasive breast cancer. In that study, the mastectomy rate 5 years later was about twice as high in women treated with brachytherapy – cumulative incidence 3.95% vs. 2.18% with WBI. The difference persisted after a multivariate adjustment, with a hazard ratio of 2.19, according to a report published May 1, 2012, in JAMA.

Moreover, short-term and long-term complications, including breast pain, were significantly more common in women who had radiation delivered by brachytherapy. Overall survival was not significantly different, however, at about 87% in both groups studied, Dr. Dr. Grace L. Smith of the University of Texas M.D. Anderson Cancer Center in Houston and her coauthors reported (JAMA 2012;307:1827-37).

In a press release asserting that the new study contradicts the JAMA report, Dr. Beitsch called attention to limitations of the M.D. Anderson study: He noted that it is based on Medicare claims data, which often do not provide an accurate clinical picture. In addition, many of the end points are "soft," poorly defined and difficult to quantify, he said, adding that the reported complication rates after breast surgery and radiotherapy vary widely, and are subject to under- or over-reporting.

Finally, "the authors’ inferences of harm to patients from breast brachytherapy are speculative," he said.

The American Society of Breast Surgeons (ASBrS) is one of three groups that previously issued rebuttals to the retrospective study. In the same press release, ASBrS executive committee member Dr. Hiram S. Cody III said that ASBrS continues to support its Consensus Statement on APBI and guidelines for patient selection, which was revised Aug. 15, 2011.

"APBI appears to be safe and effective treatment for properly selected breast conservation patients," said Dr. Cody, an attending surgeon at Memorial Sloan-Kettering Cancer Center and professor of clinical surgery at Cornell University, both in New York.

"We wish to emphasize that, although the 6-year results of APBI are encouraging, they do not conclusively establish equivalence with WBI, for which the supporting data include multiple randomized trials with follow-up exceeding 20 years, and meta-analyses that conclusively link local control and survival," Dr. Cody stated.

"APBI must ultimately be held to the same standard, and a randomized trial, NSABP [National Surgical Adjuvant Breast and Bowel Project] B-39, directly compares partial breast irradiation (by interstitial catheters, balloon devices, strut-based devices, or external beam) with WBI and promises to better define the ultimate role of APBI."

Dr. Beitsch and Dr. Cody stated that they have no disclosures.

Accelerated partial breast radiation with MammoSite balloon brachytherapy appears to control the tumor bed more effectively than whole breast irradiation, investigators reported at the annual meeting of the American Society of Breast Surgeons.

Dr. Peter Beitsch and his colleagues compared data from the society’s MammoSite Registry with prior findings from studies of whole-breast irradiation (WBI). They said the proportion of recurrences occurring in the tumor bed was much smaller with accelerated partial breast radiation (APBI) – 28% vs. about 69% in the earlier WBI data.

"While it made common sense to a lot of us that APBI should offer better rates of local control, compared to WBI, since the radiation therapy with APBI is delivered directly to the tumor site, this is the first study to have actually proven this hypothesis," Dr. Beitsch, director of the Dallas Breast Center, said in an interview.

"WBI has been held as the ‘gold standard’ for post-lumpectomy radiation therapy, and our data may change that line of thought," he added.

Randomized trials demonstrate that lumpectomy with WBI yields survival rates equivalent to those seen with mastectomy; they also show that WBI has no impact on the ipsilateral occurrence of new "elsewhere" cancers in quadrants away from the primary tumor quadrant. Dr. Beitsch explained during a press briefing.

In all such trials, thus far, tumor bed recurrence rates have been higher than were the rates of ipsilateral "elsewhere" cancers, he said.

Now, however, 5-year actuarial data from 1,449 cases in 1,440 patients in the MammoSite registry show the opposite. The patients were treated at 97 institutions between May 2002 and July 2004. Most patients, 87%, were diagnosed with invasive breast cancer and the rest, 13%, with ductal carcinoma in situ (DCIS). Median follow up was 60 months.

Dr. Beitsch reported there have been 50 (3.5%) ipsilateral breast tumor recurrences: 14 (1.0%) at the initial tumor site and 36 (2.5%) elsewhere in the breast. The total actuarial rate of ipsilateral breast tumor recurrence was 3.61% (3.65 % for invasive disease and 3.36 % for DCIS). Tumor bed recurrences accounted for 28% of all recurrences, whereas recurrences elsewhere added up to 72%.

In contrast, historical data on whole-breast irradiation (WBI) from six studies demonstrate that tumor bed recurrences are about twice as common as recurrences elsewhere, approximately 69% vs. about 31% elsewhere, said Dr. Beitsch, co-principal investigator for the registry and lead author on the study.

The new findings contrast with a controversial retrospective study of breast brachytherapy in nearly 93,000 older women with invasive breast cancer. In that study, the mastectomy rate 5 years later was about twice as high in women treated with brachytherapy – cumulative incidence 3.95% vs. 2.18% with WBI. The difference persisted after a multivariate adjustment, with a hazard ratio of 2.19, according to a report published May 1, 2012, in JAMA.

Moreover, short-term and long-term complications, including breast pain, were significantly more common in women who had radiation delivered by brachytherapy. Overall survival was not significantly different, however, at about 87% in both groups studied, Dr. Dr. Grace L. Smith of the University of Texas M.D. Anderson Cancer Center in Houston and her coauthors reported (JAMA 2012;307:1827-37).

In a press release asserting that the new study contradicts the JAMA report, Dr. Beitsch called attention to limitations of the M.D. Anderson study: He noted that it is based on Medicare claims data, which often do not provide an accurate clinical picture. In addition, many of the end points are "soft," poorly defined and difficult to quantify, he said, adding that the reported complication rates after breast surgery and radiotherapy vary widely, and are subject to under- or over-reporting.

Finally, "the authors’ inferences of harm to patients from breast brachytherapy are speculative," he said.

The American Society of Breast Surgeons (ASBrS) is one of three groups that previously issued rebuttals to the retrospective study. In the same press release, ASBrS executive committee member Dr. Hiram S. Cody III said that ASBrS continues to support its Consensus Statement on APBI and guidelines for patient selection, which was revised Aug. 15, 2011.

"APBI appears to be safe and effective treatment for properly selected breast conservation patients," said Dr. Cody, an attending surgeon at Memorial Sloan-Kettering Cancer Center and professor of clinical surgery at Cornell University, both in New York.

"We wish to emphasize that, although the 6-year results of APBI are encouraging, they do not conclusively establish equivalence with WBI, for which the supporting data include multiple randomized trials with follow-up exceeding 20 years, and meta-analyses that conclusively link local control and survival," Dr. Cody stated.

"APBI must ultimately be held to the same standard, and a randomized trial, NSABP [National Surgical Adjuvant Breast and Bowel Project] B-39, directly compares partial breast irradiation (by interstitial catheters, balloon devices, strut-based devices, or external beam) with WBI and promises to better define the ultimate role of APBI."

Dr. Beitsch and Dr. Cody stated that they have no disclosures.

Accelerated partial breast radiation with MammoSite balloon brachytherapy appears to control the tumor bed more effectively than whole breast irradiation, investigators reported at the annual meeting of the American Society of Breast Surgeons.

Dr. Peter Beitsch and his colleagues compared data from the society’s MammoSite Registry with prior findings from studies of whole-breast irradiation (WBI). They said the proportion of recurrences occurring in the tumor bed was much smaller with accelerated partial breast radiation (APBI) – 28% vs. about 69% in the earlier WBI data.

"While it made common sense to a lot of us that APBI should offer better rates of local control, compared to WBI, since the radiation therapy with APBI is delivered directly to the tumor site, this is the first study to have actually proven this hypothesis," Dr. Beitsch, director of the Dallas Breast Center, said in an interview.

"WBI has been held as the ‘gold standard’ for post-lumpectomy radiation therapy, and our data may change that line of thought," he added.

Randomized trials demonstrate that lumpectomy with WBI yields survival rates equivalent to those seen with mastectomy; they also show that WBI has no impact on the ipsilateral occurrence of new "elsewhere" cancers in quadrants away from the primary tumor quadrant. Dr. Beitsch explained during a press briefing.

In all such trials, thus far, tumor bed recurrence rates have been higher than were the rates of ipsilateral "elsewhere" cancers, he said.

Now, however, 5-year actuarial data from 1,449 cases in 1,440 patients in the MammoSite registry show the opposite. The patients were treated at 97 institutions between May 2002 and July 2004. Most patients, 87%, were diagnosed with invasive breast cancer and the rest, 13%, with ductal carcinoma in situ (DCIS). Median follow up was 60 months.

Dr. Beitsch reported there have been 50 (3.5%) ipsilateral breast tumor recurrences: 14 (1.0%) at the initial tumor site and 36 (2.5%) elsewhere in the breast. The total actuarial rate of ipsilateral breast tumor recurrence was 3.61% (3.65 % for invasive disease and 3.36 % for DCIS). Tumor bed recurrences accounted for 28% of all recurrences, whereas recurrences elsewhere added up to 72%.

In contrast, historical data on whole-breast irradiation (WBI) from six studies demonstrate that tumor bed recurrences are about twice as common as recurrences elsewhere, approximately 69% vs. about 31% elsewhere, said Dr. Beitsch, co-principal investigator for the registry and lead author on the study.

The new findings contrast with a controversial retrospective study of breast brachytherapy in nearly 93,000 older women with invasive breast cancer. In that study, the mastectomy rate 5 years later was about twice as high in women treated with brachytherapy – cumulative incidence 3.95% vs. 2.18% with WBI. The difference persisted after a multivariate adjustment, with a hazard ratio of 2.19, according to a report published May 1, 2012, in JAMA.

Moreover, short-term and long-term complications, including breast pain, were significantly more common in women who had radiation delivered by brachytherapy. Overall survival was not significantly different, however, at about 87% in both groups studied, Dr. Dr. Grace L. Smith of the University of Texas M.D. Anderson Cancer Center in Houston and her coauthors reported (JAMA 2012;307:1827-37).

In a press release asserting that the new study contradicts the JAMA report, Dr. Beitsch called attention to limitations of the M.D. Anderson study: He noted that it is based on Medicare claims data, which often do not provide an accurate clinical picture. In addition, many of the end points are "soft," poorly defined and difficult to quantify, he said, adding that the reported complication rates after breast surgery and radiotherapy vary widely, and are subject to under- or over-reporting.

Finally, "the authors’ inferences of harm to patients from breast brachytherapy are speculative," he said.

The American Society of Breast Surgeons (ASBrS) is one of three groups that previously issued rebuttals to the retrospective study. In the same press release, ASBrS executive committee member Dr. Hiram S. Cody III said that ASBrS continues to support its Consensus Statement on APBI and guidelines for patient selection, which was revised Aug. 15, 2011.

"APBI appears to be safe and effective treatment for properly selected breast conservation patients," said Dr. Cody, an attending surgeon at Memorial Sloan-Kettering Cancer Center and professor of clinical surgery at Cornell University, both in New York.

"We wish to emphasize that, although the 6-year results of APBI are encouraging, they do not conclusively establish equivalence with WBI, for which the supporting data include multiple randomized trials with follow-up exceeding 20 years, and meta-analyses that conclusively link local control and survival," Dr. Cody stated.

"APBI must ultimately be held to the same standard, and a randomized trial, NSABP [National Surgical Adjuvant Breast and Bowel Project] B-39, directly compares partial breast irradiation (by interstitial catheters, balloon devices, strut-based devices, or external beam) with WBI and promises to better define the ultimate role of APBI."

Dr. Beitsch and Dr. Cody stated that they have no disclosures.

Radiofrequency ablation could become an option for some patients facing adjuvant radiation after breast-conserving surgery for invasive breast cancer, the results of a phase II trial suggest.

Excision followed by radiofrequency ablation (eRFA) was at least as effective as radiation therapy following lumpectomy in preventing local tumor recurrence in the single-arm study of 73 patients who underwent breast conserving surgery, according to investigators. Only one patient had an in-site recurrence while three had recurrences, they reported at the annual meeting of the American Society of Breast Surgeons.

"For selected breast cancer patients undergoing breast-conservation therapy, eRFA is an attractive alternative to breast irradiation," said Dr. Misti Wilson at a press briefing.

The intraoperative procedure of excision followed by radiofrequency ablation employs heat to create an additional tumor-free zone, approximating the zone treated by brachytherapy, around the lumpectomy cavity. Its benefits include reduced likelihood of the need for re-excision and for additional radiation; lower cost, compared with radiation; and good to excellent cosmetic results, said Dr. Wilson, a breast surgical oncology fellow at the University of Arkansas in Little Rock.

The study enrolled 73 patients with tumors of less than 3 cm. Median follow-up was 55 months. All underwent standard lumpectomy followed by radiofrequency ablation, in which the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 degrees C for 15 minutes.

None of the patients received subsequent radiation or chemotherapy. Only those with grossly positive margins or residual calcifications on postoperative mammography were re-resected.

Among 19 patients who had inadequate margins, RFA spared 16 (84%) from additional surgery. Only three patients (4%) had to return to the operating room for resection because of grossly positive margins. There was just one in-site recurrence out of 73 patients, and 3 had recurrences elsewhere, Dr. Wilson reported.

Of 40 patients who scored their cosmesis, 18 (45%) reported excellent cosmetic results, 18 (45%) reported good results, and 4 (10%) reported fair cosmetic results.

"These findings show that this is a safe procedure, patients can have less repeat surgery, they have good cosmetic outcomes, and RFA may replace radiation therapy in patients with small tumors and are node negative," Dr. Wilson said in an interview.

The cost of eRFA is around $2,000 dollars. In contrast, standard whole breast radiation costs approximately $11,000, and partial breast around $18,000 depending upon site and location, she said.

The ABLATE trial is investigating eRFA in a larger patient population. To date, the trial includes five centers (Columbia University, N.Y; University of Kansas, Lawrence; Comprehensive Breast Care of San Diego, University of Arizona, Tucson; and Rockefeller Cancer Institute in Little Rock) and is actively recruiting and training additional sites.

Early results were presented in a poster by the primary investigator of both studies, Dr. V. Suzanne Klimberg, professor of surgery and pathology and director of the breast program at the University of Arkansas.

Of 55 patients (mean age 65 years) with ductal carcinoma in situ or invasive breast cancer with average tumor size 0.9 cm who underwent eRFA, 20 had positive margins: 14 had close margins (less than 2 mm), 2 had focally positive margins, and 4 had grossly positive margins. Of those, 15 were spared re-excision. Morbidity at 30 days was 7.2% and there were no deaths.

The University of Arkansas sponsored the study in collaboration with AngioDynamics, maker of the RFA delivery system.Dr. Wilson stated that she has no disclosures. Dr. Klimberg received research grants from AngioDynamics and retailers Fashion Footwear Association of New York and QVC.

Radiofrequency ablation could become an option for some patients facing adjuvant radiation after breast-conserving surgery for invasive breast cancer, the results of a phase II trial suggest.

Excision followed by radiofrequency ablation (eRFA) was at least as effective as radiation therapy following lumpectomy in preventing local tumor recurrence in the single-arm study of 73 patients who underwent breast conserving surgery, according to investigators. Only one patient had an in-site recurrence while three had recurrences, they reported at the annual meeting of the American Society of Breast Surgeons.

"For selected breast cancer patients undergoing breast-conservation therapy, eRFA is an attractive alternative to breast irradiation," said Dr. Misti Wilson at a press briefing.

The intraoperative procedure of excision followed by radiofrequency ablation employs heat to create an additional tumor-free zone, approximating the zone treated by brachytherapy, around the lumpectomy cavity. Its benefits include reduced likelihood of the need for re-excision and for additional radiation; lower cost, compared with radiation; and good to excellent cosmetic results, said Dr. Wilson, a breast surgical oncology fellow at the University of Arkansas in Little Rock.

The study enrolled 73 patients with tumors of less than 3 cm. Median follow-up was 55 months. All underwent standard lumpectomy followed by radiofrequency ablation, in which the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 degrees C for 15 minutes.

None of the patients received subsequent radiation or chemotherapy. Only those with grossly positive margins or residual calcifications on postoperative mammography were re-resected.

Among 19 patients who had inadequate margins, RFA spared 16 (84%) from additional surgery. Only three patients (4%) had to return to the operating room for resection because of grossly positive margins. There was just one in-site recurrence out of 73 patients, and 3 had recurrences elsewhere, Dr. Wilson reported.

Of 40 patients who scored their cosmesis, 18 (45%) reported excellent cosmetic results, 18 (45%) reported good results, and 4 (10%) reported fair cosmetic results.

"These findings show that this is a safe procedure, patients can have less repeat surgery, they have good cosmetic outcomes, and RFA may replace radiation therapy in patients with small tumors and are node negative," Dr. Wilson said in an interview.

The cost of eRFA is around $2,000 dollars. In contrast, standard whole breast radiation costs approximately $11,000, and partial breast around $18,000 depending upon site and location, she said.

The ABLATE trial is investigating eRFA in a larger patient population. To date, the trial includes five centers (Columbia University, N.Y; University of Kansas, Lawrence; Comprehensive Breast Care of San Diego, University of Arizona, Tucson; and Rockefeller Cancer Institute in Little Rock) and is actively recruiting and training additional sites.

Early results were presented in a poster by the primary investigator of both studies, Dr. V. Suzanne Klimberg, professor of surgery and pathology and director of the breast program at the University of Arkansas.

Of 55 patients (mean age 65 years) with ductal carcinoma in situ or invasive breast cancer with average tumor size 0.9 cm who underwent eRFA, 20 had positive margins: 14 had close margins (less than 2 mm), 2 had focally positive margins, and 4 had grossly positive margins. Of those, 15 were spared re-excision. Morbidity at 30 days was 7.2% and there were no deaths.

The University of Arkansas sponsored the study in collaboration with AngioDynamics, maker of the RFA delivery system.Dr. Wilson stated that she has no disclosures. Dr. Klimberg received research grants from AngioDynamics and retailers Fashion Footwear Association of New York and QVC.

Radiofrequency ablation could become an option for some patients facing adjuvant radiation after breast-conserving surgery for invasive breast cancer, the results of a phase II trial suggest.

Excision followed by radiofrequency ablation (eRFA) was at least as effective as radiation therapy following lumpectomy in preventing local tumor recurrence in the single-arm study of 73 patients who underwent breast conserving surgery, according to investigators. Only one patient had an in-site recurrence while three had recurrences, they reported at the annual meeting of the American Society of Breast Surgeons.

"For selected breast cancer patients undergoing breast-conservation therapy, eRFA is an attractive alternative to breast irradiation," said Dr. Misti Wilson at a press briefing.

The intraoperative procedure of excision followed by radiofrequency ablation employs heat to create an additional tumor-free zone, approximating the zone treated by brachytherapy, around the lumpectomy cavity. Its benefits include reduced likelihood of the need for re-excision and for additional radiation; lower cost, compared with radiation; and good to excellent cosmetic results, said Dr. Wilson, a breast surgical oncology fellow at the University of Arkansas in Little Rock.

The study enrolled 73 patients with tumors of less than 3 cm. Median follow-up was 55 months. All underwent standard lumpectomy followed by radiofrequency ablation, in which the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 degrees C for 15 minutes.

None of the patients received subsequent radiation or chemotherapy. Only those with grossly positive margins or residual calcifications on postoperative mammography were re-resected.

Among 19 patients who had inadequate margins, RFA spared 16 (84%) from additional surgery. Only three patients (4%) had to return to the operating room for resection because of grossly positive margins. There was just one in-site recurrence out of 73 patients, and 3 had recurrences elsewhere, Dr. Wilson reported.

Of 40 patients who scored their cosmesis, 18 (45%) reported excellent cosmetic results, 18 (45%) reported good results, and 4 (10%) reported fair cosmetic results.

"These findings show that this is a safe procedure, patients can have less repeat surgery, they have good cosmetic outcomes, and RFA may replace radiation therapy in patients with small tumors and are node negative," Dr. Wilson said in an interview.

The cost of eRFA is around $2,000 dollars. In contrast, standard whole breast radiation costs approximately $11,000, and partial breast around $18,000 depending upon site and location, she said.

The ABLATE trial is investigating eRFA in a larger patient population. To date, the trial includes five centers (Columbia University, N.Y; University of Kansas, Lawrence; Comprehensive Breast Care of San Diego, University of Arizona, Tucson; and Rockefeller Cancer Institute in Little Rock) and is actively recruiting and training additional sites.

Early results were presented in a poster by the primary investigator of both studies, Dr. V. Suzanne Klimberg, professor of surgery and pathology and director of the breast program at the University of Arkansas.

Of 55 patients (mean age 65 years) with ductal carcinoma in situ or invasive breast cancer with average tumor size 0.9 cm who underwent eRFA, 20 had positive margins: 14 had close margins (less than 2 mm), 2 had focally positive margins, and 4 had grossly positive margins. Of those, 15 were spared re-excision. Morbidity at 30 days was 7.2% and there were no deaths.

The University of Arkansas sponsored the study in collaboration with AngioDynamics, maker of the RFA delivery system.Dr. Wilson stated that she has no disclosures. Dr. Klimberg received research grants from AngioDynamics and retailers Fashion Footwear Association of New York and QVC.

ORLANDO – Surgery for ductal carcinoma in situ, with or without adjuvant therapy, saves lives, asserted a breast cancer surgeon at a symposium sponsored by the Society of Surgical Oncology.

Following a surgical biopsy alone, about half of all cases of low-grade ductal carcinoma in situ (DCIS) will progress to invasive cancer within an average of 10-15 years, said Dr. Kimberly J. Van Zee, a surgical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

Additionally, without intervention, low-grade DCIS will result in death from ipsilateral invasive recurrence of breast cancer in about 18% of patients, Dr. Van Zee said.

"With treatment of DCIS, whether it’s breast conservation or mastectomy, with or without radiation, breast cancer–specific survival is over 95%," she noted.

The incidence of DCIS has increased steadily since 1975, when the rate was slightly more than 5 in 100,000 women. In 2009, the rate had reached approximately 36 in 100,000, according to Surveillance, Epidemiology, and End Results (SEER) data. The increase is probably a result of the growing adoption of screening mammography over the same period, Dr. Van Zee commented.

Treatment trends for DCIS showed a gradual but steady decline in mastectomy – from 70% in 1983 to about 28% in 1999 – and a corresponding increase in breast-conserving treatment, which increased from about 25% to 68% over the same period.

Beginning around 2005, however, there was evidence that the trend was reversing, with upticks in both mastectomy for unilateral breast cancer (J. Clin. Oncol. 2010;28:3437-41) and contralateral prophylactic mastectomy, both among women with invasive cancers and DCIS (Ann. Surg. Oncol. 2010;17:2554-62). The trends paralleled the rise in screening mammography in the United States and elsewhere in the world.

The gradual but steady decline in breast cancer deaths that began in the early 1990s appears to be attributable to a combination of increased screening mammography and improvements in adjuvant therapy, Dr. Van Zee noted, citing a 2005 study (N. Engl. J. Med. 2005;353:1784-92).

"They dissected all the various effects of treatment, incidence of screening-detected diseases, etc., and all their analyses concluded that about half of the reduction in death rate was due to screening and the other half was due to adjuvant therapy. So I think this is good circumstantial evidence that screening, with its resultant increased incidence in DCIS and the resulting increased treatment of DCIS, does result in a lower death rate from breast cancer," she said.

Further evidence comes from studies in which pathologists reviewed thousands of slides of biopsy-acquired breast tissue originally reported as benign. In each study (Cancer 1980;46[4 Suppl]:919-25; Cancer 2005;103:2481-84), the investigator identified about 30 samples with evidence of low-grade, relatively low-volume DCIS that was not recognized or treated. After 20-30 years of follow-up, half of the women had developed a clinically apparent ipsilateral breast cancer recurrence. The majority of tumors were invasive. In the second study, the authors noted that 5 of the 28 women (18%) with previously undetected DCIS died of breast cancer.

Evidence from a meta-analysis (Cancer 1999;85:616-28) suggests that the risk for invasive recurrence following a mastectomy for DCIS is 1.1%, and that the risk for breast cancer death is less than 1.1%.

The risk for distant recurrence and/or death from breast-conserving surgery with or without adjuvant radiotherapy in prospective randomized trials of radiotherapy for DCIS was less than 5%. Among patients with invasive local failure in those trials, however, 18%-25% developed metastatic disease, indicating the importance of avoiding local recurrence.

Mastectomy and breast-conserving surgery combined with radiotherapy and/or endocrine therapy all provide excellent disease-specific and overall survival results, Dr. Van Zee said.

"The goal should be avoiding local recurrence and, in particular, invasive recurrence, minimizing morbidity, and perhaps individualizing the treatment to the disease. One could consider age, comorbidities, [and] life expectancy, and weigh those against the morbidity of the treatment and the risk of local recurrence," she said.

Dr. Van Zee reported no relevant financial disclosures.

ORLANDO – Surgery for ductal carcinoma in situ, with or without adjuvant therapy, saves lives, asserted a breast cancer surgeon at a symposium sponsored by the Society of Surgical Oncology.

Following a surgical biopsy alone, about half of all cases of low-grade ductal carcinoma in situ (DCIS) will progress to invasive cancer within an average of 10-15 years, said Dr. Kimberly J. Van Zee, a surgical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

Additionally, without intervention, low-grade DCIS will result in death from ipsilateral invasive recurrence of breast cancer in about 18% of patients, Dr. Van Zee said.

"With treatment of DCIS, whether it’s breast conservation or mastectomy, with or without radiation, breast cancer–specific survival is over 95%," she noted.

The incidence of DCIS has increased steadily since 1975, when the rate was slightly more than 5 in 100,000 women. In 2009, the rate had reached approximately 36 in 100,000, according to Surveillance, Epidemiology, and End Results (SEER) data. The increase is probably a result of the growing adoption of screening mammography over the same period, Dr. Van Zee commented.

Treatment trends for DCIS showed a gradual but steady decline in mastectomy – from 70% in 1983 to about 28% in 1999 – and a corresponding increase in breast-conserving treatment, which increased from about 25% to 68% over the same period.

Beginning around 2005, however, there was evidence that the trend was reversing, with upticks in both mastectomy for unilateral breast cancer (J. Clin. Oncol. 2010;28:3437-41) and contralateral prophylactic mastectomy, both among women with invasive cancers and DCIS (Ann. Surg. Oncol. 2010;17:2554-62). The trends paralleled the rise in screening mammography in the United States and elsewhere in the world.

The gradual but steady decline in breast cancer deaths that began in the early 1990s appears to be attributable to a combination of increased screening mammography and improvements in adjuvant therapy, Dr. Van Zee noted, citing a 2005 study (N. Engl. J. Med. 2005;353:1784-92).

"They dissected all the various effects of treatment, incidence of screening-detected diseases, etc., and all their analyses concluded that about half of the reduction in death rate was due to screening and the other half was due to adjuvant therapy. So I think this is good circumstantial evidence that screening, with its resultant increased incidence in DCIS and the resulting increased treatment of DCIS, does result in a lower death rate from breast cancer," she said.

Further evidence comes from studies in which pathologists reviewed thousands of slides of biopsy-acquired breast tissue originally reported as benign. In each study (Cancer 1980;46[4 Suppl]:919-25; Cancer 2005;103:2481-84), the investigator identified about 30 samples with evidence of low-grade, relatively low-volume DCIS that was not recognized or treated. After 20-30 years of follow-up, half of the women had developed a clinically apparent ipsilateral breast cancer recurrence. The majority of tumors were invasive. In the second study, the authors noted that 5 of the 28 women (18%) with previously undetected DCIS died of breast cancer.

Evidence from a meta-analysis (Cancer 1999;85:616-28) suggests that the risk for invasive recurrence following a mastectomy for DCIS is 1.1%, and that the risk for breast cancer death is less than 1.1%.

The risk for distant recurrence and/or death from breast-conserving surgery with or without adjuvant radiotherapy in prospective randomized trials of radiotherapy for DCIS was less than 5%. Among patients with invasive local failure in those trials, however, 18%-25% developed metastatic disease, indicating the importance of avoiding local recurrence.

Mastectomy and breast-conserving surgery combined with radiotherapy and/or endocrine therapy all provide excellent disease-specific and overall survival results, Dr. Van Zee said.

"The goal should be avoiding local recurrence and, in particular, invasive recurrence, minimizing morbidity, and perhaps individualizing the treatment to the disease. One could consider age, comorbidities, [and] life expectancy, and weigh those against the morbidity of the treatment and the risk of local recurrence," she said.

Dr. Van Zee reported no relevant financial disclosures.

ORLANDO – Surgery for ductal carcinoma in situ, with or without adjuvant therapy, saves lives, asserted a breast cancer surgeon at a symposium sponsored by the Society of Surgical Oncology.

Following a surgical biopsy alone, about half of all cases of low-grade ductal carcinoma in situ (DCIS) will progress to invasive cancer within an average of 10-15 years, said Dr. Kimberly J. Van Zee, a surgical oncologist at Memorial Sloan-Kettering Cancer Center in New York.

Additionally, without intervention, low-grade DCIS will result in death from ipsilateral invasive recurrence of breast cancer in about 18% of patients, Dr. Van Zee said.

"With treatment of DCIS, whether it’s breast conservation or mastectomy, with or without radiation, breast cancer–specific survival is over 95%," she noted.

The incidence of DCIS has increased steadily since 1975, when the rate was slightly more than 5 in 100,000 women. In 2009, the rate had reached approximately 36 in 100,000, according to Surveillance, Epidemiology, and End Results (SEER) data. The increase is probably a result of the growing adoption of screening mammography over the same period, Dr. Van Zee commented.

Treatment trends for DCIS showed a gradual but steady decline in mastectomy – from 70% in 1983 to about 28% in 1999 – and a corresponding increase in breast-conserving treatment, which increased from about 25% to 68% over the same period.

Beginning around 2005, however, there was evidence that the trend was reversing, with upticks in both mastectomy for unilateral breast cancer (J. Clin. Oncol. 2010;28:3437-41) and contralateral prophylactic mastectomy, both among women with invasive cancers and DCIS (Ann. Surg. Oncol. 2010;17:2554-62). The trends paralleled the rise in screening mammography in the United States and elsewhere in the world.

The gradual but steady decline in breast cancer deaths that began in the early 1990s appears to be attributable to a combination of increased screening mammography and improvements in adjuvant therapy, Dr. Van Zee noted, citing a 2005 study (N. Engl. J. Med. 2005;353:1784-92).

"They dissected all the various effects of treatment, incidence of screening-detected diseases, etc., and all their analyses concluded that about half of the reduction in death rate was due to screening and the other half was due to adjuvant therapy. So I think this is good circumstantial evidence that screening, with its resultant increased incidence in DCIS and the resulting increased treatment of DCIS, does result in a lower death rate from breast cancer," she said.

Further evidence comes from studies in which pathologists reviewed thousands of slides of biopsy-acquired breast tissue originally reported as benign. In each study (Cancer 1980;46[4 Suppl]:919-25; Cancer 2005;103:2481-84), the investigator identified about 30 samples with evidence of low-grade, relatively low-volume DCIS that was not recognized or treated. After 20-30 years of follow-up, half of the women had developed a clinically apparent ipsilateral breast cancer recurrence. The majority of tumors were invasive. In the second study, the authors noted that 5 of the 28 women (18%) with previously undetected DCIS died of breast cancer.

Evidence from a meta-analysis (Cancer 1999;85:616-28) suggests that the risk for invasive recurrence following a mastectomy for DCIS is 1.1%, and that the risk for breast cancer death is less than 1.1%.

The risk for distant recurrence and/or death from breast-conserving surgery with or without adjuvant radiotherapy in prospective randomized trials of radiotherapy for DCIS was less than 5%. Among patients with invasive local failure in those trials, however, 18%-25% developed metastatic disease, indicating the importance of avoiding local recurrence.

Mastectomy and breast-conserving surgery combined with radiotherapy and/or endocrine therapy all provide excellent disease-specific and overall survival results, Dr. Van Zee said.

"The goal should be avoiding local recurrence and, in particular, invasive recurrence, minimizing morbidity, and perhaps individualizing the treatment to the disease. One could consider age, comorbidities, [and] life expectancy, and weigh those against the morbidity of the treatment and the risk of local recurrence," she said.

Dr. Van Zee reported no relevant financial disclosures.

Infrared thermography did not accurately predict malignancy and produced an unacceptably high false-positive rate in women with radiologic abnormalities requiring breast biopsy in a 2-year prospective study.

The No-Touch Breast Scan (NTBS) is a noninvasive, non–radiation-based imaging tool that measures and compares thermal abnormalities in breasts using dual infrared cameras and computer analysis. It generates a score that reflects blood flow patterns based on the theory of tumor angiogenesis.

The technology is being explored as an alternative to radiation-based imaging in women at risk for breast cancer and as a way to reduce the number of benign biopsies, Dr. Andrea V. Barrio said during a press briefing at the annual meeting of the American Society of Breast Surgeons.

This study evaluated NTBS screening as a predictor of breast cancer in patients undergoing minimally invasive breast biopsy for suspicious mammogram, ultrasound, or MRI findings.

But the results demonstrated that NTBS "cannot be used as a successful adjunct to mammography, nor can it replace any of the screening modalities that are standard practice. Mammography remains the gold standard for breast cancer screening," said Dr. Barrio, an attending breast surgeon at Bryn Mawr (Pa.) Hospital.

"I think the utility of NTBS remains unclear. For the purposes of our study, NTBS could not discriminate between benign and malignant lesions in the low-specificity mode, and the high-sensitivity mode resulted in an unacceptable number of false-positive results," she added in an interview.

A total of 181 women (median age at diagnosis 52.5 years) with 187 abnormal radiologic findings were evaluated from October 2009 to May 2011. Each patient had an NTBS prior to tissue biopsy, and final tissue pathologies were compared with the corresponding NTBS scan results. Each breast was interpreted as positive or negative based on computer analysis of thermal abnormalities. The contralateral breast was scanned in all patients.

Prior to Oct. 15, 2010, patients were initially scanned using a "high-specificity" NTBS mode termed NTBS1. Subsequently a "high-sensitivity mode (NTBS2)" was used to minimize false-negative results. Following initial data analysis, all patients were retrospectively re-evaluated in the NTBS2 mode.

Of the 181 patients initially evaluated, 3 were excluded due to a nonductal or lobular breast malignancy, leaving a total of 178 patients. Of those, 50 had 52 positive breast biopsies and 128 had 132 negative biopsies.

Of the 52 positive biopsies, only 26 had a positive NTBS, giving a sensitivity of just 50%. The sensitivity of NTBS was even lower in the 20 in situ cancers, compared with the 32 invasive cancers (35% vs. 59%, respectively), Dr. Barrio reported.

Of the 132 negative biopsies, 88 had negative NTBS scans, giving a 67% specificity. "The positive predictive value of NTBS was 37% and the negative predictive value was 77%," the study results showed.

Of 173 normal contralateral breasts that were scanned, 42 (24%) had a positive NTBS scan.

Among the 178 patients retrospectively evaluated using NTBS2, 22 were excluded because of an uninterpretable scan. Of the remaining 156 patients, 44 had 46 positive breast biopsies and 112 had 116 negative biopsies. Forty of the 46 positive biopsies matched a positive NTBS (sensitivity 87%).

Sensitivity was not appreciably different between in situ and invasive cancers in the NTBS2 mode (88% vs. 86%, respectively), she said.

Of the 116 negative biopsies, 55 had a negative NTBS, giving a specificity of just 48%. "The positive predictive value of NTBS2 was 40% and the negative predictive value was 90%," the study reported. Of the 151 normal contralateral breasts that were scanned, 72 (47%) had a positive reading.

In the interview, Dr. Barrio said that her group is not seeking a replacement for mammography, as it is a cost-efficient screening tool that has been proven to decrease mortality from breast cancer.

However, "we are looking for studies to supplement mammography, in order to address its limitations, i.e., dense breasts. I think molecular breast imaging in particular shows a lot of promise for the future in women with dense breasts."

This study was funded by the Humler Oncology fund. Dr. Barrio had no other disclosures.

Infrared thermography did not accurately predict malignancy and produced an unacceptably high false-positive rate in women with radiologic abnormalities requiring breast biopsy in a 2-year prospective study.

The No-Touch Breast Scan (NTBS) is a noninvasive, non–radiation-based imaging tool that measures and compares thermal abnormalities in breasts using dual infrared cameras and computer analysis. It generates a score that reflects blood flow patterns based on the theory of tumor angiogenesis.

The technology is being explored as an alternative to radiation-based imaging in women at risk for breast cancer and as a way to reduce the number of benign biopsies, Dr. Andrea V. Barrio said during a press briefing at the annual meeting of the American Society of Breast Surgeons.

This study evaluated NTBS screening as a predictor of breast cancer in patients undergoing minimally invasive breast biopsy for suspicious mammogram, ultrasound, or MRI findings.

But the results demonstrated that NTBS "cannot be used as a successful adjunct to mammography, nor can it replace any of the screening modalities that are standard practice. Mammography remains the gold standard for breast cancer screening," said Dr. Barrio, an attending breast surgeon at Bryn Mawr (Pa.) Hospital.

"I think the utility of NTBS remains unclear. For the purposes of our study, NTBS could not discriminate between benign and malignant lesions in the low-specificity mode, and the high-sensitivity mode resulted in an unacceptable number of false-positive results," she added in an interview.

A total of 181 women (median age at diagnosis 52.5 years) with 187 abnormal radiologic findings were evaluated from October 2009 to May 2011. Each patient had an NTBS prior to tissue biopsy, and final tissue pathologies were compared with the corresponding NTBS scan results. Each breast was interpreted as positive or negative based on computer analysis of thermal abnormalities. The contralateral breast was scanned in all patients.

Prior to Oct. 15, 2010, patients were initially scanned using a "high-specificity" NTBS mode termed NTBS1. Subsequently a "high-sensitivity mode (NTBS2)" was used to minimize false-negative results. Following initial data analysis, all patients were retrospectively re-evaluated in the NTBS2 mode.

Of the 181 patients initially evaluated, 3 were excluded due to a nonductal or lobular breast malignancy, leaving a total of 178 patients. Of those, 50 had 52 positive breast biopsies and 128 had 132 negative biopsies.

Of the 52 positive biopsies, only 26 had a positive NTBS, giving a sensitivity of just 50%. The sensitivity of NTBS was even lower in the 20 in situ cancers, compared with the 32 invasive cancers (35% vs. 59%, respectively), Dr. Barrio reported.

Of the 132 negative biopsies, 88 had negative NTBS scans, giving a 67% specificity. "The positive predictive value of NTBS was 37% and the negative predictive value was 77%," the study results showed.

Of 173 normal contralateral breasts that were scanned, 42 (24%) had a positive NTBS scan.

Among the 178 patients retrospectively evaluated using NTBS2, 22 were excluded because of an uninterpretable scan. Of the remaining 156 patients, 44 had 46 positive breast biopsies and 112 had 116 negative biopsies. Forty of the 46 positive biopsies matched a positive NTBS (sensitivity 87%).

Sensitivity was not appreciably different between in situ and invasive cancers in the NTBS2 mode (88% vs. 86%, respectively), she said.

Of the 116 negative biopsies, 55 had a negative NTBS, giving a specificity of just 48%. "The positive predictive value of NTBS2 was 40% and the negative predictive value was 90%," the study reported. Of the 151 normal contralateral breasts that were scanned, 72 (47%) had a positive reading.

In the interview, Dr. Barrio said that her group is not seeking a replacement for mammography, as it is a cost-efficient screening tool that has been proven to decrease mortality from breast cancer.

However, "we are looking for studies to supplement mammography, in order to address its limitations, i.e., dense breasts. I think molecular breast imaging in particular shows a lot of promise for the future in women with dense breasts."

This study was funded by the Humler Oncology fund. Dr. Barrio had no other disclosures.

Infrared thermography did not accurately predict malignancy and produced an unacceptably high false-positive rate in women with radiologic abnormalities requiring breast biopsy in a 2-year prospective study.

The No-Touch Breast Scan (NTBS) is a noninvasive, non–radiation-based imaging tool that measures and compares thermal abnormalities in breasts using dual infrared cameras and computer analysis. It generates a score that reflects blood flow patterns based on the theory of tumor angiogenesis.

The technology is being explored as an alternative to radiation-based imaging in women at risk for breast cancer and as a way to reduce the number of benign biopsies, Dr. Andrea V. Barrio said during a press briefing at the annual meeting of the American Society of Breast Surgeons.

This study evaluated NTBS screening as a predictor of breast cancer in patients undergoing minimally invasive breast biopsy for suspicious mammogram, ultrasound, or MRI findings.

But the results demonstrated that NTBS "cannot be used as a successful adjunct to mammography, nor can it replace any of the screening modalities that are standard practice. Mammography remains the gold standard for breast cancer screening," said Dr. Barrio, an attending breast surgeon at Bryn Mawr (Pa.) Hospital.

"I think the utility of NTBS remains unclear. For the purposes of our study, NTBS could not discriminate between benign and malignant lesions in the low-specificity mode, and the high-sensitivity mode resulted in an unacceptable number of false-positive results," she added in an interview.

A total of 181 women (median age at diagnosis 52.5 years) with 187 abnormal radiologic findings were evaluated from October 2009 to May 2011. Each patient had an NTBS prior to tissue biopsy, and final tissue pathologies were compared with the corresponding NTBS scan results. Each breast was interpreted as positive or negative based on computer analysis of thermal abnormalities. The contralateral breast was scanned in all patients.

Prior to Oct. 15, 2010, patients were initially scanned using a "high-specificity" NTBS mode termed NTBS1. Subsequently a "high-sensitivity mode (NTBS2)" was used to minimize false-negative results. Following initial data analysis, all patients were retrospectively re-evaluated in the NTBS2 mode.

Of the 181 patients initially evaluated, 3 were excluded due to a nonductal or lobular breast malignancy, leaving a total of 178 patients. Of those, 50 had 52 positive breast biopsies and 128 had 132 negative biopsies.

Of the 52 positive biopsies, only 26 had a positive NTBS, giving a sensitivity of just 50%. The sensitivity of NTBS was even lower in the 20 in situ cancers, compared with the 32 invasive cancers (35% vs. 59%, respectively), Dr. Barrio reported.

Of the 132 negative biopsies, 88 had negative NTBS scans, giving a 67% specificity. "The positive predictive value of NTBS was 37% and the negative predictive value was 77%," the study results showed.

Of 173 normal contralateral breasts that were scanned, 42 (24%) had a positive NTBS scan.

Among the 178 patients retrospectively evaluated using NTBS2, 22 were excluded because of an uninterpretable scan. Of the remaining 156 patients, 44 had 46 positive breast biopsies and 112 had 116 negative biopsies. Forty of the 46 positive biopsies matched a positive NTBS (sensitivity 87%).

Sensitivity was not appreciably different between in situ and invasive cancers in the NTBS2 mode (88% vs. 86%, respectively), she said.

Of the 116 negative biopsies, 55 had a negative NTBS, giving a specificity of just 48%. "The positive predictive value of NTBS2 was 40% and the negative predictive value was 90%," the study reported. Of the 151 normal contralateral breasts that were scanned, 72 (47%) had a positive reading.

In the interview, Dr. Barrio said that her group is not seeking a replacement for mammography, as it is a cost-efficient screening tool that has been proven to decrease mortality from breast cancer.

However, "we are looking for studies to supplement mammography, in order to address its limitations, i.e., dense breasts. I think molecular breast imaging in particular shows a lot of promise for the future in women with dense breasts."

This study was funded by the Humler Oncology fund. Dr. Barrio had no other disclosures.

Men with breast cancer died more than 2 years sooner than did women with the condition, in the largest-ever study of male breast cancer, investigators reported.

Male breast cancer patients presented with more advanced disease and had lower 5-year survival rates as well as shorter median overall survival than did women, Dr. Jon M. Greif said at the annual meeting of the American Society of Breast Surgeons.

They were less likely to have radiation therapy or partial mastectomy, but chemotherapy rates were not significantly different, said Dr. Greif, a breast surgeon who practices in Oakland, Calif.

The data come from an analysis of 13,457 men – representing 0.9% of all breast cancers – and 1,439,866 women with breast cancer in the National Cancer Data Base spanning the years 1998 through 2007. The explanation for the differences in overall survival is most likely multifactorial, according to Dr. Greif.

"Certainly, one reason is that with well accepted screening for female breast cancer, and heightened awareness amongst women, female breast cancer is detected earlier. Evidence from our study is that male breast cancer is larger and more likely to have spread to lymph nodes and beyond when first discovered," he said in an interview.

"However, male breast cancer was less likely to be low grade, and this would be a biological difference. And, finally, men were older, and more likely to die of other causes."

Men at particularly high risk should have careful clinical examinations annually, and consider annual screening mammography, advised Dr. Greif. Among those at high risk, he included men with known gene mutations that increase their risk (BRCA and Klinefelter’s syndrome, for example), men who have been treated or otherwise exposed to high levels of radiation to the chest, men with previous breast cancer, and men with strong family histories of male or female breast cancer.

"Currently, breast cancer in men is found as a palpable retro- or periareolar mass, a nipple discharge or crusting, skin erosion, or palpable lymph nodes. Examination of the retroareolar and periareolar tissues for lumps and/or skin changes should be a part of every man’s annual physical exam, and men should check occasionally themselves," Dr. Greif said.

Five-year overall survival was 83% for women with breast cancer (median survival 129 months) and 74% for men (median 101 months), a highly statistically significant difference (P less than. 0001), he reported.

A comparison of overall survival by stages showed significantly better outcomes for women with early disease, but similar outcomes in more advanced disease. Females had significantly better 5-year survival rates (P less than .0001) for stage 0 (94% vs. 90%), stage I (90% vs. 87%) and stage II (82% vs. 74%) breast cancer. No significant differences were seen in 5-year survival for stage III (56.9% vs. 56.5%, P = .99) or stage IV (19% vs. 16%, P = .20).

The following findings also were reported:

– Men with breast cancer were more often African American (11.7% vs. 9.9%, odds ratio 1.19), less often Hispanic (3.6% vs. 4.5%, OR 0.74), and older (63 vs. 59 years old).

– Men had larger tumors (median 20.0 vs. 15.0 mm), were less likely to have grade 1 tumors (16.0% vs. 20.7%), were more likely to have lymph node metastasis (41.9% vs. 33.2%, OR 1.45), and were more likely to have distant metastasis (4% vs. 3%, OR 1.39).

– Men were less likely to have lobular carcinoma (10% vs. 18%, OR 0.51) and more likely to be estrogen receptor positive (88.3% vs. 78.2%, OR 2.10) and progesterone receptor positive (76.8% vs. 67.0%, OR 1.63).

– Men were less likely to have been treated with a partial mastectomy (33% vs. 62%, OR 0.31) and less likely to have received radiation (35.9% vs. 50.4%, OR 0.55).

All of these differences were highly statistically significant, with P values less than .0001. However, the differences may not have been of clinical significance, the investigators said, citing the large numbers of cases.

The proportions of men and women receiving chemotherapy were similar (40.1% vs. 39.8%, OR 1.01, P = .40) and only small differences were seen in hormonal therapy rates (41.2% vs. 42.4%, OR 0.95, P = .006).

Treatment of male breast cancer is similar to that of female breast cancer, according to Dr. Greif. Nearly all male breast cancers are hormone receptor positive, so treatment with antiestrogenic endocrine therapy should be a part of the adjuvant treatment of nearly all male breast cancer.

Chemotherapy should be considered for tumors with higher risk of systemic return, he said. For tumors with risk of locoregional return, including those that are large and/or have lymph node involvement, adjuvant radiation should be part of the treatment.

The surgery for male breast cancer is almost always total mastectomy, he noted, and there is evidence that sentinel lymph node biopsy works for male breast cancer as well as in female breast cancer.

This study was funded in part by Alta Bates Summit Medical Center. None of the authors have any conflicts of interest or financial disclosures.

Men with breast cancer died more than 2 years sooner than did women with the condition, in the largest-ever study of male breast cancer, investigators reported.

Male breast cancer patients presented with more advanced disease and had lower 5-year survival rates as well as shorter median overall survival than did women, Dr. Jon M. Greif said at the annual meeting of the American Society of Breast Surgeons.

They were less likely to have radiation therapy or partial mastectomy, but chemotherapy rates were not significantly different, said Dr. Greif, a breast surgeon who practices in Oakland, Calif.

The data come from an analysis of 13,457 men – representing 0.9% of all breast cancers – and 1,439,866 women with breast cancer in the National Cancer Data Base spanning the years 1998 through 2007. The explanation for the differences in overall survival is most likely multifactorial, according to Dr. Greif.

"Certainly, one reason is that with well accepted screening for female breast cancer, and heightened awareness amongst women, female breast cancer is detected earlier. Evidence from our study is that male breast cancer is larger and more likely to have spread to lymph nodes and beyond when first discovered," he said in an interview.

"However, male breast cancer was less likely to be low grade, and this would be a biological difference. And, finally, men were older, and more likely to die of other causes."

Men at particularly high risk should have careful clinical examinations annually, and consider annual screening mammography, advised Dr. Greif. Among those at high risk, he included men with known gene mutations that increase their risk (BRCA and Klinefelter’s syndrome, for example), men who have been treated or otherwise exposed to high levels of radiation to the chest, men with previous breast cancer, and men with strong family histories of male or female breast cancer.

"Currently, breast cancer in men is found as a palpable retro- or periareolar mass, a nipple discharge or crusting, skin erosion, or palpable lymph nodes. Examination of the retroareolar and periareolar tissues for lumps and/or skin changes should be a part of every man’s annual physical exam, and men should check occasionally themselves," Dr. Greif said.

Five-year overall survival was 83% for women with breast cancer (median survival 129 months) and 74% for men (median 101 months), a highly statistically significant difference (P less than. 0001), he reported.

A comparison of overall survival by stages showed significantly better outcomes for women with early disease, but similar outcomes in more advanced disease. Females had significantly better 5-year survival rates (P less than .0001) for stage 0 (94% vs. 90%), stage I (90% vs. 87%) and stage II (82% vs. 74%) breast cancer. No significant differences were seen in 5-year survival for stage III (56.9% vs. 56.5%, P = .99) or stage IV (19% vs. 16%, P = .20).

The following findings also were reported:

– Men with breast cancer were more often African American (11.7% vs. 9.9%, odds ratio 1.19), less often Hispanic (3.6% vs. 4.5%, OR 0.74), and older (63 vs. 59 years old).

– Men had larger tumors (median 20.0 vs. 15.0 mm), were less likely to have grade 1 tumors (16.0% vs. 20.7%), were more likely to have lymph node metastasis (41.9% vs. 33.2%, OR 1.45), and were more likely to have distant metastasis (4% vs. 3%, OR 1.39).

– Men were less likely to have lobular carcinoma (10% vs. 18%, OR 0.51) and more likely to be estrogen receptor positive (88.3% vs. 78.2%, OR 2.10) and progesterone receptor positive (76.8% vs. 67.0%, OR 1.63).

– Men were less likely to have been treated with a partial mastectomy (33% vs. 62%, OR 0.31) and less likely to have received radiation (35.9% vs. 50.4%, OR 0.55).

All of these differences were highly statistically significant, with P values less than .0001. However, the differences may not have been of clinical significance, the investigators said, citing the large numbers of cases.

The proportions of men and women receiving chemotherapy were similar (40.1% vs. 39.8%, OR 1.01, P = .40) and only small differences were seen in hormonal therapy rates (41.2% vs. 42.4%, OR 0.95, P = .006).

Treatment of male breast cancer is similar to that of female breast cancer, according to Dr. Greif. Nearly all male breast cancers are hormone receptor positive, so treatment with antiestrogenic endocrine therapy should be a part of the adjuvant treatment of nearly all male breast cancer.

Chemotherapy should be considered for tumors with higher risk of systemic return, he said. For tumors with risk of locoregional return, including those that are large and/or have lymph node involvement, adjuvant radiation should be part of the treatment.

The surgery for male breast cancer is almost always total mastectomy, he noted, and there is evidence that sentinel lymph node biopsy works for male breast cancer as well as in female breast cancer.

This study was funded in part by Alta Bates Summit Medical Center. None of the authors have any conflicts of interest or financial disclosures.

Men with breast cancer died more than 2 years sooner than did women with the condition, in the largest-ever study of male breast cancer, investigators reported.

Male breast cancer patients presented with more advanced disease and had lower 5-year survival rates as well as shorter median overall survival than did women, Dr. Jon M. Greif said at the annual meeting of the American Society of Breast Surgeons.

They were less likely to have radiation therapy or partial mastectomy, but chemotherapy rates were not significantly different, said Dr. Greif, a breast surgeon who practices in Oakland, Calif.

The data come from an analysis of 13,457 men – representing 0.9% of all breast cancers – and 1,439,866 women with breast cancer in the National Cancer Data Base spanning the years 1998 through 2007. The explanation for the differences in overall survival is most likely multifactorial, according to Dr. Greif.

"Certainly, one reason is that with well accepted screening for female breast cancer, and heightened awareness amongst women, female breast cancer is detected earlier. Evidence from our study is that male breast cancer is larger and more likely to have spread to lymph nodes and beyond when first discovered," he said in an interview.

"However, male breast cancer was less likely to be low grade, and this would be a biological difference. And, finally, men were older, and more likely to die of other causes."

Men at particularly high risk should have careful clinical examinations annually, and consider annual screening mammography, advised Dr. Greif. Among those at high risk, he included men with known gene mutations that increase their risk (BRCA and Klinefelter’s syndrome, for example), men who have been treated or otherwise exposed to high levels of radiation to the chest, men with previous breast cancer, and men with strong family histories of male or female breast cancer.

"Currently, breast cancer in men is found as a palpable retro- or periareolar mass, a nipple discharge or crusting, skin erosion, or palpable lymph nodes. Examination of the retroareolar and periareolar tissues for lumps and/or skin changes should be a part of every man’s annual physical exam, and men should check occasionally themselves," Dr. Greif said.

Five-year overall survival was 83% for women with breast cancer (median survival 129 months) and 74% for men (median 101 months), a highly statistically significant difference (P less than. 0001), he reported.

A comparison of overall survival by stages showed significantly better outcomes for women with early disease, but similar outcomes in more advanced disease. Females had significantly better 5-year survival rates (P less than .0001) for stage 0 (94% vs. 90%), stage I (90% vs. 87%) and stage II (82% vs. 74%) breast cancer. No significant differences were seen in 5-year survival for stage III (56.9% vs. 56.5%, P = .99) or stage IV (19% vs. 16%, P = .20).

The following findings also were reported:

– Men with breast cancer were more often African American (11.7% vs. 9.9%, odds ratio 1.19), less often Hispanic (3.6% vs. 4.5%, OR 0.74), and older (63 vs. 59 years old).

– Men had larger tumors (median 20.0 vs. 15.0 mm), were less likely to have grade 1 tumors (16.0% vs. 20.7%), were more likely to have lymph node metastasis (41.9% vs. 33.2%, OR 1.45), and were more likely to have distant metastasis (4% vs. 3%, OR 1.39).

– Men were less likely to have lobular carcinoma (10% vs. 18%, OR 0.51) and more likely to be estrogen receptor positive (88.3% vs. 78.2%, OR 2.10) and progesterone receptor positive (76.8% vs. 67.0%, OR 1.63).

– Men were less likely to have been treated with a partial mastectomy (33% vs. 62%, OR 0.31) and less likely to have received radiation (35.9% vs. 50.4%, OR 0.55).

All of these differences were highly statistically significant, with P values less than .0001. However, the differences may not have been of clinical significance, the investigators said, citing the large numbers of cases.

The proportions of men and women receiving chemotherapy were similar (40.1% vs. 39.8%, OR 1.01, P = .40) and only small differences were seen in hormonal therapy rates (41.2% vs. 42.4%, OR 0.95, P = .006).

Treatment of male breast cancer is similar to that of female breast cancer, according to Dr. Greif. Nearly all male breast cancers are hormone receptor positive, so treatment with antiestrogenic endocrine therapy should be a part of the adjuvant treatment of nearly all male breast cancer.

Chemotherapy should be considered for tumors with higher risk of systemic return, he said. For tumors with risk of locoregional return, including those that are large and/or have lymph node involvement, adjuvant radiation should be part of the treatment.

The surgery for male breast cancer is almost always total mastectomy, he noted, and there is evidence that sentinel lymph node biopsy works for male breast cancer as well as in female breast cancer.

This study was funded in part by Alta Bates Summit Medical Center. None of the authors have any conflicts of interest or financial disclosures.

A retrospective study of nearly 93,000 older women with invasive breast cancer suggests that brachytherapy after lumpectomy leads to more complications and more subsequent mastectomies than does postoperative whole-breast radiation.

The mastectomy rate 5 years later was about twice as high in women treated with brachytherapy – cumulative incidence 3.95% vs. 2.18% with whole-breast radiation (WBI) – and the difference persisted after a multivariate adjustment, with a hazard ratio of 2.19, according to a report published May 1, 2012 in JAMA.

Moreover, short-term and long-term complications, including breast pain, were significantly more common in women who had radiation delivered by brachytherapy. Overall survival was not significantly different, however, at about 87% in both groups studied.

What this means is that for every 56 women treated with brachytherapy, 1 woman was harmed with an unnecessary mastectomy (absolute excess risk, 1.77%), wrote Dr. Grace L. Smith of the University of Texas M.D. Anderson Cancer Center in Houston and her coauthors. At 1 year, 1 woman suffered an unnecessary postoperative complication for every 9 women treated with brachytherapy (absolute excess risk, 10.64%), and by 5 years, 1 woman for every 16 was harmed by an unnecessary postoperative radiation complication (absolute excess risk, 6.16%).

"Potential public health implications of these findings are substantial, given the high incidence of breast cancer, along with the recent rapid increase in breast brachytherapy use. Although these results await validation in the prospective setting, they also prompt caution over widespread application of breast brachytherapy outside the study setting," the authors concluded (JAMA 2012;307:1827-37).

An earlier version of the study stirred controversy when principal investigator Dr. Benjamin D. Smith, also of M.D. Anderson, presented it at the San Antonio Breast Cancer Symposium in December 2011. Three professional societies – the American Society for Radiation Oncology (ASTRO), American Society of Breast Surgeons, and American Brachytherapy Society – issued rebuttals soon after.

Among the objections raised were the retrospective nature of the study, limitations inherent in studies based on Medicare claims data, and the fact that the data did not take into account improvements in brachytherapy technology since the study years of 2000-2007. Definitive results from ongoing randomized trials comparing the safety and efficacy of brachytherapy and standard WBI are still years off, critics said, citing the ongoing phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 trial.

For the current study, the investigators identified 92,735 women aged 67 years or older who had incident invasive breast cancer diagnosed between 2003 and 2007 and were followed through 2008. After lumpectomy, a large majority of the women studied, 85,783 (92.5%), underwent WBI, while 6,952 (7.5%) were treated with brachytherapy.

At 1 year, infectious skin or soft tissue infections were significantly more frequent with brachytherapy (16.20% vs. 10.33% with WBI), as were noninfectious postoperative complications (16.25% vs. 9.0%).

By 5 years, the cumulative incidence of breast pain reached 14.55% with brachytherapy, compared with 11.92% with WBI. Fat necrosis (8.26% vs. 4.05%) and rib fracture (4.53% vs. 3.62%) also occurred at higher rates in the brachytherapy group.

Dr. Smith was supported by a Multidisciplinary Postdoctoral Award from the Department of Defense. Coauthors Dr. Benjamin D. Smith and Dr. Sharon H. Giordano were supported by a grant from the Cancer Prevention and Research Institute of Texas. Dr. Ya-Chen Tina Shih was supported by grants from the Agency for Healthcare Research and Quality, the National Cancer Institute, and the University of Chicago Cancer Research Foundation Women’s Board. This study also was supported in part by grants from the National Cancer Institute and by a philanthropic gift from Ann and Clarence Cazalot.

A retrospective study of nearly 93,000 older women with invasive breast cancer suggests that brachytherapy after lumpectomy leads to more complications and more subsequent mastectomies than does postoperative whole-breast radiation.

The mastectomy rate 5 years later was about twice as high in women treated with brachytherapy – cumulative incidence 3.95% vs. 2.18% with whole-breast radiation (WBI) – and the difference persisted after a multivariate adjustment, with a hazard ratio of 2.19, according to a report published May 1, 2012 in JAMA.

Moreover, short-term and long-term complications, including breast pain, were significantly more common in women who had radiation delivered by brachytherapy. Overall survival was not significantly different, however, at about 87% in both groups studied.

What this means is that for every 56 women treated with brachytherapy, 1 woman was harmed with an unnecessary mastectomy (absolute excess risk, 1.77%), wrote Dr. Grace L. Smith of the University of Texas M.D. Anderson Cancer Center in Houston and her coauthors. At 1 year, 1 woman suffered an unnecessary postoperative complication for every 9 women treated with brachytherapy (absolute excess risk, 10.64%), and by 5 years, 1 woman for every 16 was harmed by an unnecessary postoperative radiation complication (absolute excess risk, 6.16%).

"Potential public health implications of these findings are substantial, given the high incidence of breast cancer, along with the recent rapid increase in breast brachytherapy use. Although these results await validation in the prospective setting, they also prompt caution over widespread application of breast brachytherapy outside the study setting," the authors concluded (JAMA 2012;307:1827-37).

An earlier version of the study stirred controversy when principal investigator Dr. Benjamin D. Smith, also of M.D. Anderson, presented it at the San Antonio Breast Cancer Symposium in December 2011. Three professional societies – the American Society for Radiation Oncology (ASTRO), American Society of Breast Surgeons, and American Brachytherapy Society – issued rebuttals soon after.

Among the objections raised were the retrospective nature of the study, limitations inherent in studies based on Medicare claims data, and the fact that the data did not take into account improvements in brachytherapy technology since the study years of 2000-2007. Definitive results from ongoing randomized trials comparing the safety and efficacy of brachytherapy and standard WBI are still years off, critics said, citing the ongoing phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 trial.

For the current study, the investigators identified 92,735 women aged 67 years or older who had incident invasive breast cancer diagnosed between 2003 and 2007 and were followed through 2008. After lumpectomy, a large majority of the women studied, 85,783 (92.5%), underwent WBI, while 6,952 (7.5%) were treated with brachytherapy.

At 1 year, infectious skin or soft tissue infections were significantly more frequent with brachytherapy (16.20% vs. 10.33% with WBI), as were noninfectious postoperative complications (16.25% vs. 9.0%).

By 5 years, the cumulative incidence of breast pain reached 14.55% with brachytherapy, compared with 11.92% with WBI. Fat necrosis (8.26% vs. 4.05%) and rib fracture (4.53% vs. 3.62%) also occurred at higher rates in the brachytherapy group.

Dr. Smith was supported by a Multidisciplinary Postdoctoral Award from the Department of Defense. Coauthors Dr. Benjamin D. Smith and Dr. Sharon H. Giordano were supported by a grant from the Cancer Prevention and Research Institute of Texas. Dr. Ya-Chen Tina Shih was supported by grants from the Agency for Healthcare Research and Quality, the National Cancer Institute, and the University of Chicago Cancer Research Foundation Women’s Board. This study also was supported in part by grants from the National Cancer Institute and by a philanthropic gift from Ann and Clarence Cazalot.

A retrospective study of nearly 93,000 older women with invasive breast cancer suggests that brachytherapy after lumpectomy leads to more complications and more subsequent mastectomies than does postoperative whole-breast radiation.

The mastectomy rate 5 years later was about twice as high in women treated with brachytherapy – cumulative incidence 3.95% vs. 2.18% with whole-breast radiation (WBI) – and the difference persisted after a multivariate adjustment, with a hazard ratio of 2.19, according to a report published May 1, 2012 in JAMA.

Moreover, short-term and long-term complications, including breast pain, were significantly more common in women who had radiation delivered by brachytherapy. Overall survival was not significantly different, however, at about 87% in both groups studied.

What this means is that for every 56 women treated with brachytherapy, 1 woman was harmed with an unnecessary mastectomy (absolute excess risk, 1.77%), wrote Dr. Grace L. Smith of the University of Texas M.D. Anderson Cancer Center in Houston and her coauthors. At 1 year, 1 woman suffered an unnecessary postoperative complication for every 9 women treated with brachytherapy (absolute excess risk, 10.64%), and by 5 years, 1 woman for every 16 was harmed by an unnecessary postoperative radiation complication (absolute excess risk, 6.16%).

"Potential public health implications of these findings are substantial, given the high incidence of breast cancer, along with the recent rapid increase in breast brachytherapy use. Although these results await validation in the prospective setting, they also prompt caution over widespread application of breast brachytherapy outside the study setting," the authors concluded (JAMA 2012;307:1827-37).

An earlier version of the study stirred controversy when principal investigator Dr. Benjamin D. Smith, also of M.D. Anderson, presented it at the San Antonio Breast Cancer Symposium in December 2011. Three professional societies – the American Society for Radiation Oncology (ASTRO), American Society of Breast Surgeons, and American Brachytherapy Society – issued rebuttals soon after.

Among the objections raised were the retrospective nature of the study, limitations inherent in studies based on Medicare claims data, and the fact that the data did not take into account improvements in brachytherapy technology since the study years of 2000-2007. Definitive results from ongoing randomized trials comparing the safety and efficacy of brachytherapy and standard WBI are still years off, critics said, citing the ongoing phase III National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 trial.

For the current study, the investigators identified 92,735 women aged 67 years or older who had incident invasive breast cancer diagnosed between 2003 and 2007 and were followed through 2008. After lumpectomy, a large majority of the women studied, 85,783 (92.5%), underwent WBI, while 6,952 (7.5%) were treated with brachytherapy.

At 1 year, infectious skin or soft tissue infections were significantly more frequent with brachytherapy (16.20% vs. 10.33% with WBI), as were noninfectious postoperative complications (16.25% vs. 9.0%).

By 5 years, the cumulative incidence of breast pain reached 14.55% with brachytherapy, compared with 11.92% with WBI. Fat necrosis (8.26% vs. 4.05%) and rib fracture (4.53% vs. 3.62%) also occurred at higher rates in the brachytherapy group.

Dr. Smith was supported by a Multidisciplinary Postdoctoral Award from the Department of Defense. Coauthors Dr. Benjamin D. Smith and Dr. Sharon H. Giordano were supported by a grant from the Cancer Prevention and Research Institute of Texas. Dr. Ya-Chen Tina Shih was supported by grants from the Agency for Healthcare Research and Quality, the National Cancer Institute, and the University of Chicago Cancer Research Foundation Women’s Board. This study also was supported in part by grants from the National Cancer Institute and by a philanthropic gift from Ann and Clarence Cazalot.

The Food and Drug Administration has identified another batch of counterfeit bevacizumab in the United States, bringing with it concerns for physicians about their legal liability in the complex world of foreign-supplied drugs.

Agency lab tests confirmed that vials of Roche’s Altuzan 400 mg/16mL – a brand of bevacizumab approved in Turkey – contain no active ingredient, the FDA announced early in April. The only bevacizumab brand approved in the United States is Avastin, a product distributed by Roche-owned Genentech.

Subsequently, the agency sent letters to specific physicians in 13 states, who are believed to have purchased medications from foreign or unlicensed suppliers that sold illegal prescription medications. These medical practices "are putting patients at risk of exposure to medications that may be counterfeit, contaminated, improperly stored and transported, ineffective, and dangerous," the agency warned in the letters.

"Even if the identified drugs were not counterfeit, Altuzan is not approved by FDA for use in the United States. ... In virtually all cases, purchasing unapproved prescription drugs from foreign sources violates the Federal Food, Drug, and Cosmetic Act and is illegal," it advised the recipients.

Physicians Could Face Malpractice Suits

This language raises questions about physician liability when drugs are obtained from foreign distributors that have not been approved by the FDA. Not only do concerns about safety come into play, but intellectual property rights do as well, according to Dr. Maxwell Gregg Bloche, who is a physician, a professor of law, and codirector of the Georgetown–Johns Hopkins Joint Program in Law and Public Health.

Dr. Bloche emphasized a distinction between "the vast majority of prescriptions, which are not being supplied in the office" and those such as bevacizumab that are delivered in the context of a medical practice. In the former, the physician – acting as an enforcer of intellectual property law – could be acting against the interests of patients who might suffer terrible health consequences as a result of not being able to afford the drug. "However, when it comes to known counterfeit drugs that could be seriously dangerous, the physician’s role is to safeguard the patient," he said in an interview.

Adding complexity to the situation is an array of FDA-approved foreign suppliers, those foreign companies that knowingly supply dangerous or ineffective drugs, and a third category of suppliers that fall in between.

Outside the United States, there are reputable, high-quality pharmaceutical companies that offer generic drugs at much lower cost, noted Dr. Bloche. However, these companies often do not recognize U.S. patent laws. Only the name-brand drugs are legally available in the United States, until the FDA approves generic versions of those drugs.

"The physician is responsible for making medically sound judgments about risk," he said. If a patient mentions getting a prescribed drug from a foreign source, the physician can indicate that the source produces high-quality, generic versions. The patient may be breaking U.S. laws by doing so; the physician merely offered an opinion.

State malpractice laws come into play once the FDA has identified foreign suppliers that are selling counterfeit drugs – as in this round of counterfeit bevacizumab – and has warned physicians and the public, according to Dr. Bloche. Any physician who is still prescribing and/or using the drug for patients, or who tells the patient that the drug is safe, is then potentially liable.

"I think the medical malpractice law is the one that most physicians are going to be afraid of, which is a state tort law issue, said Dr. Bloche.

In recent months, one oncologist has been prosecuted on charges of distributing and receiving "misbranded and adulterated" prescription drugs in a case brought by the United States Attorney’s Office for the Eastern District of Missouri. Dr. Abid S. Nisar pleaded guilty to one count of "misbranding drugs," according to a government statement. The legal action was part of a larger case involving Neupogen, Herceptin, and Rituxan, but not Avastin, and a distributor known as Ban Dune Marketing Inc. (BDMI).

Buy From a Reputable Distributor

For practicing oncologist Dr. Patrick W. Cobb, "the main way that you know that you’re getting the right thing is to buy it from a reputable distributor. ... When we start looking outside of the large distributors, that’s when you run into problems," said Dr. Cobb, managing partner at Frontier Cancer Center in Billings, Montana, and former president of the Community Oncology Alliance.

When a drug is procured and given directly to a patient by a physician – as is the case with many oncology drugs – "the only safe move is for the physician to follow U.S. law, because then the physician is liable," Dr. Cobb said in an interview.

"When you’re an oncologist administering these kinds of drugs, you just can’t take that chance. You want to make sure that what you give the patient is exactly the drug and exactly the dosage."

In its first fake-bevacizumab warning, the FDA said that 19 U.S. medical practices obtained the counterfeit from Quality Specialty Products (QSP), a foreign supplier also known as Montana Health Care Solutions. QSP products are also distributed by Volunteer Distribution in Gainesboro, Tenn.

The agency specified medications purchased from a foreign distributor named Richards Pharma, also known as Richards Services, Warwick Healthcare Solutions, or Ban Dune Marketing Inc. (BDMI) in its more recent letter alerting oncologists to the second counterfeit.

"Packaging or vials found in the [United States] that claim to be Roche’s Altuzan with lot number B6021 should be considered counterfeit," the agency wrote. The counterfeit version of Altuzan contains "no active ingredient."

Other drugs already obtained from these sources are also suspect, according to the letter. "Many, if not all, of the products sold and distributed through this distributor have not been approved by the FDA," the agency said.

What the FDA Wants Physicians to Do

The FDA advised physicians to stop using these products and to contact the FDA. The products should be retained and securely stored until further notice by the FDA. The agency recommends that physicians take the following actions:

• Report adverse events related to the use of suspect injectable cancer medicines to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

• Verify that a supplier is licensed in a particular state by going to the Drug Integrity and Supply Chain Security section of www.fda.gov for a list of state websites and contacts where this information can be found.

• Report suspected counterfeit products to the FDA Office of Criminal Investigations (OCI) at 800-551-3989, or by e-mail to DrugSupplyChainIntegrity@fda.hhs.gov.

Dr. Bloche and Dr. Cobb said they have no relevant conflicts of interest.

The Food and Drug Administration has identified another batch of counterfeit bevacizumab in the United States, bringing with it concerns for physicians about their legal liability in the complex world of foreign-supplied drugs.

Agency lab tests confirmed that vials of Roche’s Altuzan 400 mg/16mL – a brand of bevacizumab approved in Turkey – contain no active ingredient, the FDA announced early in April. The only bevacizumab brand approved in the United States is Avastin, a product distributed by Roche-owned Genentech.

Subsequently, the agency sent letters to specific physicians in 13 states, who are believed to have purchased medications from foreign or unlicensed suppliers that sold illegal prescription medications. These medical practices "are putting patients at risk of exposure to medications that may be counterfeit, contaminated, improperly stored and transported, ineffective, and dangerous," the agency warned in the letters.

"Even if the identified drugs were not counterfeit, Altuzan is not approved by FDA for use in the United States. ... In virtually all cases, purchasing unapproved prescription drugs from foreign sources violates the Federal Food, Drug, and Cosmetic Act and is illegal," it advised the recipients.

Physicians Could Face Malpractice Suits

This language raises questions about physician liability when drugs are obtained from foreign distributors that have not been approved by the FDA. Not only do concerns about safety come into play, but intellectual property rights do as well, according to Dr. Maxwell Gregg Bloche, who is a physician, a professor of law, and codirector of the Georgetown–Johns Hopkins Joint Program in Law and Public Health.

Dr. Bloche emphasized a distinction between "the vast majority of prescriptions, which are not being supplied in the office" and those such as bevacizumab that are delivered in the context of a medical practice. In the former, the physician – acting as an enforcer of intellectual property law – could be acting against the interests of patients who might suffer terrible health consequences as a result of not being able to afford the drug. "However, when it comes to known counterfeit drugs that could be seriously dangerous, the physician’s role is to safeguard the patient," he said in an interview.

Adding complexity to the situation is an array of FDA-approved foreign suppliers, those foreign companies that knowingly supply dangerous or ineffective drugs, and a third category of suppliers that fall in between.

Outside the United States, there are reputable, high-quality pharmaceutical companies that offer generic drugs at much lower cost, noted Dr. Bloche. However, these companies often do not recognize U.S. patent laws. Only the name-brand drugs are legally available in the United States, until the FDA approves generic versions of those drugs.

"The physician is responsible for making medically sound judgments about risk," he said. If a patient mentions getting a prescribed drug from a foreign source, the physician can indicate that the source produces high-quality, generic versions. The patient may be breaking U.S. laws by doing so; the physician merely offered an opinion.

State malpractice laws come into play once the FDA has identified foreign suppliers that are selling counterfeit drugs – as in this round of counterfeit bevacizumab – and has warned physicians and the public, according to Dr. Bloche. Any physician who is still prescribing and/or using the drug for patients, or who tells the patient that the drug is safe, is then potentially liable.

"I think the medical malpractice law is the one that most physicians are going to be afraid of, which is a state tort law issue, said Dr. Bloche.

In recent months, one oncologist has been prosecuted on charges of distributing and receiving "misbranded and adulterated" prescription drugs in a case brought by the United States Attorney’s Office for the Eastern District of Missouri. Dr. Abid S. Nisar pleaded guilty to one count of "misbranding drugs," according to a government statement. The legal action was part of a larger case involving Neupogen, Herceptin, and Rituxan, but not Avastin, and a distributor known as Ban Dune Marketing Inc. (BDMI).

Buy From a Reputable Distributor

For practicing oncologist Dr. Patrick W. Cobb, "the main way that you know that you’re getting the right thing is to buy it from a reputable distributor. ... When we start looking outside of the large distributors, that’s when you run into problems," said Dr. Cobb, managing partner at Frontier Cancer Center in Billings, Montana, and former president of the Community Oncology Alliance.

When a drug is procured and given directly to a patient by a physician – as is the case with many oncology drugs – "the only safe move is for the physician to follow U.S. law, because then the physician is liable," Dr. Cobb said in an interview.

"When you’re an oncologist administering these kinds of drugs, you just can’t take that chance. You want to make sure that what you give the patient is exactly the drug and exactly the dosage."

In its first fake-bevacizumab warning, the FDA said that 19 U.S. medical practices obtained the counterfeit from Quality Specialty Products (QSP), a foreign supplier also known as Montana Health Care Solutions. QSP products are also distributed by Volunteer Distribution in Gainesboro, Tenn.

The agency specified medications purchased from a foreign distributor named Richards Pharma, also known as Richards Services, Warwick Healthcare Solutions, or Ban Dune Marketing Inc. (BDMI) in its more recent letter alerting oncologists to the second counterfeit.

"Packaging or vials found in the [United States] that claim to be Roche’s Altuzan with lot number B6021 should be considered counterfeit," the agency wrote. The counterfeit version of Altuzan contains "no active ingredient."

Other drugs already obtained from these sources are also suspect, according to the letter. "Many, if not all, of the products sold and distributed through this distributor have not been approved by the FDA," the agency said.

What the FDA Wants Physicians to Do

The FDA advised physicians to stop using these products and to contact the FDA. The products should be retained and securely stored until further notice by the FDA. The agency recommends that physicians take the following actions:

• Report adverse events related to the use of suspect injectable cancer medicines to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

• Verify that a supplier is licensed in a particular state by going to the Drug Integrity and Supply Chain Security section of www.fda.gov for a list of state websites and contacts where this information can be found.

• Report suspected counterfeit products to the FDA Office of Criminal Investigations (OCI) at 800-551-3989, or by e-mail to DrugSupplyChainIntegrity@fda.hhs.gov.

Dr. Bloche and Dr. Cobb said they have no relevant conflicts of interest.

The Food and Drug Administration has identified another batch of counterfeit bevacizumab in the United States, bringing with it concerns for physicians about their legal liability in the complex world of foreign-supplied drugs.

Agency lab tests confirmed that vials of Roche’s Altuzan 400 mg/16mL – a brand of bevacizumab approved in Turkey – contain no active ingredient, the FDA announced early in April. The only bevacizumab brand approved in the United States is Avastin, a product distributed by Roche-owned Genentech.

Subsequently, the agency sent letters to specific physicians in 13 states, who are believed to have purchased medications from foreign or unlicensed suppliers that sold illegal prescription medications. These medical practices "are putting patients at risk of exposure to medications that may be counterfeit, contaminated, improperly stored and transported, ineffective, and dangerous," the agency warned in the letters.

"Even if the identified drugs were not counterfeit, Altuzan is not approved by FDA for use in the United States. ... In virtually all cases, purchasing unapproved prescription drugs from foreign sources violates the Federal Food, Drug, and Cosmetic Act and is illegal," it advised the recipients.

Physicians Could Face Malpractice Suits

This language raises questions about physician liability when drugs are obtained from foreign distributors that have not been approved by the FDA. Not only do concerns about safety come into play, but intellectual property rights do as well, according to Dr. Maxwell Gregg Bloche, who is a physician, a professor of law, and codirector of the Georgetown–Johns Hopkins Joint Program in Law and Public Health.

Dr. Bloche emphasized a distinction between "the vast majority of prescriptions, which are not being supplied in the office" and those such as bevacizumab that are delivered in the context of a medical practice. In the former, the physician – acting as an enforcer of intellectual property law – could be acting against the interests of patients who might suffer terrible health consequences as a result of not being able to afford the drug. "However, when it comes to known counterfeit drugs that could be seriously dangerous, the physician’s role is to safeguard the patient," he said in an interview.

Adding complexity to the situation is an array of FDA-approved foreign suppliers, those foreign companies that knowingly supply dangerous or ineffective drugs, and a third category of suppliers that fall in between.

Outside the United States, there are reputable, high-quality pharmaceutical companies that offer generic drugs at much lower cost, noted Dr. Bloche. However, these companies often do not recognize U.S. patent laws. Only the name-brand drugs are legally available in the United States, until the FDA approves generic versions of those drugs.

"The physician is responsible for making medically sound judgments about risk," he said. If a patient mentions getting a prescribed drug from a foreign source, the physician can indicate that the source produces high-quality, generic versions. The patient may be breaking U.S. laws by doing so; the physician merely offered an opinion.

State malpractice laws come into play once the FDA has identified foreign suppliers that are selling counterfeit drugs – as in this round of counterfeit bevacizumab – and has warned physicians and the public, according to Dr. Bloche. Any physician who is still prescribing and/or using the drug for patients, or who tells the patient that the drug is safe, is then potentially liable.

"I think the medical malpractice law is the one that most physicians are going to be afraid of, which is a state tort law issue, said Dr. Bloche.

In recent months, one oncologist has been prosecuted on charges of distributing and receiving "misbranded and adulterated" prescription drugs in a case brought by the United States Attorney’s Office for the Eastern District of Missouri. Dr. Abid S. Nisar pleaded guilty to one count of "misbranding drugs," according to a government statement. The legal action was part of a larger case involving Neupogen, Herceptin, and Rituxan, but not Avastin, and a distributor known as Ban Dune Marketing Inc. (BDMI).

Buy From a Reputable Distributor

For practicing oncologist Dr. Patrick W. Cobb, "the main way that you know that you’re getting the right thing is to buy it from a reputable distributor. ... When we start looking outside of the large distributors, that’s when you run into problems," said Dr. Cobb, managing partner at Frontier Cancer Center in Billings, Montana, and former president of the Community Oncology Alliance.

When a drug is procured and given directly to a patient by a physician – as is the case with many oncology drugs – "the only safe move is for the physician to follow U.S. law, because then the physician is liable," Dr. Cobb said in an interview.

"When you’re an oncologist administering these kinds of drugs, you just can’t take that chance. You want to make sure that what you give the patient is exactly the drug and exactly the dosage."

In its first fake-bevacizumab warning, the FDA said that 19 U.S. medical practices obtained the counterfeit from Quality Specialty Products (QSP), a foreign supplier also known as Montana Health Care Solutions. QSP products are also distributed by Volunteer Distribution in Gainesboro, Tenn.

The agency specified medications purchased from a foreign distributor named Richards Pharma, also known as Richards Services, Warwick Healthcare Solutions, or Ban Dune Marketing Inc. (BDMI) in its more recent letter alerting oncologists to the second counterfeit.

"Packaging or vials found in the [United States] that claim to be Roche’s Altuzan with lot number B6021 should be considered counterfeit," the agency wrote. The counterfeit version of Altuzan contains "no active ingredient."

Other drugs already obtained from these sources are also suspect, according to the letter. "Many, if not all, of the products sold and distributed through this distributor have not been approved by the FDA," the agency said.

What the FDA Wants Physicians to Do

The FDA advised physicians to stop using these products and to contact the FDA. The products should be retained and securely stored until further notice by the FDA. The agency recommends that physicians take the following actions:

• Report adverse events related to the use of suspect injectable cancer medicines to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

• Verify that a supplier is licensed in a particular state by going to the Drug Integrity and Supply Chain Security section of www.fda.gov for a list of state websites and contacts where this information can be found.

• Report suspected counterfeit products to the FDA Office of Criminal Investigations (OCI) at 800-551-3989, or by e-mail to DrugSupplyChainIntegrity@fda.hhs.gov.

Dr. Bloche and Dr. Cobb said they have no relevant conflicts of interest.