Clinical Edge Journal Scan

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive early breast cancer, trastuzumab emtansine vs. trastuzumab is associated with longer invasive disease-free survival (DFS) regardless of the type of neoadjuvant chemotherapy (NACT) received.

Major finding: Trastuzumab emtansine was associated with longer invasive DFS vs. trastuzumab in high-risk patients (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.39-0.64), in patients who received anthracycline-based NACT (HR, 0.51; 95% CI, 0.38-0.67), and in those who received nonanthracycline-based NACT (HR, 0.43; 95% CI, 0.22-0.82).

Study details: This is a subgroup analysis of the KATHERINE trial comparing trastuzumab emtansine with trastuzumab in 1,486 HER2-positive patients with early breast cancer.

Disclosure: This study was funded by F. Hoffmann-La Roche Ltd. The authors received consulting fees, speaker bureau fees, honoraria, educational support, research funding, travel expenses, royalties from, and/or owned stocks in various organizations outside this work. Dr. Boulet was an employee of Parexel International GmbH contracted by F. Hoffmann-La Roche Ltd. Dr. Liu, Dr. Tesarowski, Dr. Lam, Dr. Song, and Dr. Smitt were/are employees of Genetech and/or owned stocks in Roche. All other authors declared no conflicts of interest.

Source: Mamounas EP et al. Ann Oncol. 2021 Apr 28. doi: 10.1016/j.annonc.2021.04.011.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive early breast cancer, trastuzumab emtansine vs. trastuzumab is associated with longer invasive disease-free survival (DFS) regardless of the type of neoadjuvant chemotherapy (NACT) received.

Major finding: Trastuzumab emtansine was associated with longer invasive DFS vs. trastuzumab in high-risk patients (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.39-0.64), in patients who received anthracycline-based NACT (HR, 0.51; 95% CI, 0.38-0.67), and in those who received nonanthracycline-based NACT (HR, 0.43; 95% CI, 0.22-0.82).

Study details: This is a subgroup analysis of the KATHERINE trial comparing trastuzumab emtansine with trastuzumab in 1,486 HER2-positive patients with early breast cancer.

Disclosure: This study was funded by F. Hoffmann-La Roche Ltd. The authors received consulting fees, speaker bureau fees, honoraria, educational support, research funding, travel expenses, royalties from, and/or owned stocks in various organizations outside this work. Dr. Boulet was an employee of Parexel International GmbH contracted by F. Hoffmann-La Roche Ltd. Dr. Liu, Dr. Tesarowski, Dr. Lam, Dr. Song, and Dr. Smitt were/are employees of Genetech and/or owned stocks in Roche. All other authors declared no conflicts of interest.

Source: Mamounas EP et al. Ann Oncol. 2021 Apr 28. doi: 10.1016/j.annonc.2021.04.011.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive early breast cancer, trastuzumab emtansine vs. trastuzumab is associated with longer invasive disease-free survival (DFS) regardless of the type of neoadjuvant chemotherapy (NACT) received.

Major finding: Trastuzumab emtansine was associated with longer invasive DFS vs. trastuzumab in high-risk patients (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.39-0.64), in patients who received anthracycline-based NACT (HR, 0.51; 95% CI, 0.38-0.67), and in those who received nonanthracycline-based NACT (HR, 0.43; 95% CI, 0.22-0.82).

Study details: This is a subgroup analysis of the KATHERINE trial comparing trastuzumab emtansine with trastuzumab in 1,486 HER2-positive patients with early breast cancer.

Disclosure: This study was funded by F. Hoffmann-La Roche Ltd. The authors received consulting fees, speaker bureau fees, honoraria, educational support, research funding, travel expenses, royalties from, and/or owned stocks in various organizations outside this work. Dr. Boulet was an employee of Parexel International GmbH contracted by F. Hoffmann-La Roche Ltd. Dr. Liu, Dr. Tesarowski, Dr. Lam, Dr. Song, and Dr. Smitt were/are employees of Genetech and/or owned stocks in Roche. All other authors declared no conflicts of interest.

Source: Mamounas EP et al. Ann Oncol. 2021 Apr 28. doi: 10.1016/j.annonc.2021.04.011.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer and progressive brain metastases despite radiotherapy, pertuzumab in combination with high-dose trastuzumab shows modest central nervous system (CNS) response and good clinical benefit.

Major finding: The confirmed CNS objective response rate was 11% with all partial responses. The clinical benefit rate at 4 months was 68% and at 6 months was 51%. The grade 3-4 adverse event rate was 44%. There were no new safety signals.

Study details: A phase 2 PATRICIA study evaluated pertuzumab in combination with high-dose trastuzumab in 39 patients with HER2-positive metastatic breast cancer and progressive brain metastases despite radiotherapy.

Disclosures: The study was sponsored by F. Hoffmann-La Roche/ Genentech. The authors received consulting/advisory fees, research funding, royalties, and travel/accommodation expenses from various sources. Dr. Fung, Dr. Cheng, and Dr. Kirschbrown reported employment by, stocks, and other ownership interests in Genentech/Roche.

Source: Lin NU et al. J Clin Oncol. 2021 May 4. doi: 10.1200/JCO.20.02822.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer and progressive brain metastases despite radiotherapy, pertuzumab in combination with high-dose trastuzumab shows modest central nervous system (CNS) response and good clinical benefit.

Major finding: The confirmed CNS objective response rate was 11% with all partial responses. The clinical benefit rate at 4 months was 68% and at 6 months was 51%. The grade 3-4 adverse event rate was 44%. There were no new safety signals.

Study details: A phase 2 PATRICIA study evaluated pertuzumab in combination with high-dose trastuzumab in 39 patients with HER2-positive metastatic breast cancer and progressive brain metastases despite radiotherapy.

Disclosures: The study was sponsored by F. Hoffmann-La Roche/ Genentech. The authors received consulting/advisory fees, research funding, royalties, and travel/accommodation expenses from various sources. Dr. Fung, Dr. Cheng, and Dr. Kirschbrown reported employment by, stocks, and other ownership interests in Genentech/Roche.

Source: Lin NU et al. J Clin Oncol. 2021 May 4. doi: 10.1200/JCO.20.02822.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer and progressive brain metastases despite radiotherapy, pertuzumab in combination with high-dose trastuzumab shows modest central nervous system (CNS) response and good clinical benefit.

Major finding: The confirmed CNS objective response rate was 11% with all partial responses. The clinical benefit rate at 4 months was 68% and at 6 months was 51%. The grade 3-4 adverse event rate was 44%. There were no new safety signals.

Study details: A phase 2 PATRICIA study evaluated pertuzumab in combination with high-dose trastuzumab in 39 patients with HER2-positive metastatic breast cancer and progressive brain metastases despite radiotherapy.

Disclosures: The study was sponsored by F. Hoffmann-La Roche/ Genentech. The authors received consulting/advisory fees, research funding, royalties, and travel/accommodation expenses from various sources. Dr. Fung, Dr. Cheng, and Dr. Kirschbrown reported employment by, stocks, and other ownership interests in Genentech/Roche.

Source: Lin NU et al. J Clin Oncol. 2021 May 4. doi: 10.1200/JCO.20.02822.

Key clinical point: Immediate reconstruction after neoadjuvant chemotherapy in women with T4 breast cancer is associated with higher odds for complication resulting in unplanned reoperations and a longer time to postmastectomy radiotherapy.

Major finding: Unplanned reoperations for complications were more common after immediate vs. delayed and no reconstruction (22% vs. 7.3% and 4.4%, respectively; P less than .001). The median time to initiation of postmastectomy radiotherapy was longer after immediate reconstruction vs. delayed and no reconstruction (60 days vs. 42 days and 49 days, respectively; P less than .001). The median time to the first recurrence was 18 months and was not significantly different between the groups (P = .13).

Study details: A retrospective study of 269 consecutive women with stage T4 breast cancer treated with surgery, chemotherapy, and radiotherapy between 2007 and 2019.

Disclosure: This study was supported in part by the National Institutes of Health. Dr. Morrow received speaking honoraria from Roche. The other authors did not disclose any conflicts of interest.

Source: Pawloski KR et al. J Am Coll Surg. 2021 Apr 24. doi: 10.1016/j.jamcollsurg.2021.04.016.

Key clinical point: Immediate reconstruction after neoadjuvant chemotherapy in women with T4 breast cancer is associated with higher odds for complication resulting in unplanned reoperations and a longer time to postmastectomy radiotherapy.

Major finding: Unplanned reoperations for complications were more common after immediate vs. delayed and no reconstruction (22% vs. 7.3% and 4.4%, respectively; P less than .001). The median time to initiation of postmastectomy radiotherapy was longer after immediate reconstruction vs. delayed and no reconstruction (60 days vs. 42 days and 49 days, respectively; P less than .001). The median time to the first recurrence was 18 months and was not significantly different between the groups (P = .13).

Study details: A retrospective study of 269 consecutive women with stage T4 breast cancer treated with surgery, chemotherapy, and radiotherapy between 2007 and 2019.

Disclosure: This study was supported in part by the National Institutes of Health. Dr. Morrow received speaking honoraria from Roche. The other authors did not disclose any conflicts of interest.

Source: Pawloski KR et al. J Am Coll Surg. 2021 Apr 24. doi: 10.1016/j.jamcollsurg.2021.04.016.

Key clinical point: Immediate reconstruction after neoadjuvant chemotherapy in women with T4 breast cancer is associated with higher odds for complication resulting in unplanned reoperations and a longer time to postmastectomy radiotherapy.

Major finding: Unplanned reoperations for complications were more common after immediate vs. delayed and no reconstruction (22% vs. 7.3% and 4.4%, respectively; P less than .001). The median time to initiation of postmastectomy radiotherapy was longer after immediate reconstruction vs. delayed and no reconstruction (60 days vs. 42 days and 49 days, respectively; P less than .001). The median time to the first recurrence was 18 months and was not significantly different between the groups (P = .13).

Study details: A retrospective study of 269 consecutive women with stage T4 breast cancer treated with surgery, chemotherapy, and radiotherapy between 2007 and 2019.

Disclosure: This study was supported in part by the National Institutes of Health. Dr. Morrow received speaking honoraria from Roche. The other authors did not disclose any conflicts of interest.

Source: Pawloski KR et al. J Am Coll Surg. 2021 Apr 24. doi: 10.1016/j.jamcollsurg.2021.04.016.

Key clinical point: The presence and extent of coronary artery calcium (CAC), as automatically quantified on routinely performed computed tomography scans, are associated with cardiovascular and coronary artery diseases.

Major finding: The risk for cardiovascular disease increased with a higher CAC score (adjusted hazard ratio, 1.8, 2.1, and 3.4 for CAC scores 11-100, 101-400, and greater than 400, respectively). The risk for coronary artery disease also increased with an increase in CAC score (adjusted hazard ratio, 2.8, 4.3, and 7.8 for CAC scores 11-100, 101-400, and greater than 400, respectively).

Study details: A multicenter cohort study of 15,915 patients with breast cancer who received radiotherapy between 2005 and 2016. The CAC scores were automatically extracted from computed tomography scans using a deep learning algorithm.

Disclosure: This study was funded by the Dutch Cancer Society. The authors received grants, lecture fees, and research support from various sources. Dr. Leiner and Dr. Isgum owned shares of Quantib-U BV and/or a patent with royalties planned. No other conflicts of interest were reported.

Source: Gal R et al. JAMA Oncol. 2021 May 6. doi: 10.1001/jamaoncol.2021.1144.

Key clinical point: The presence and extent of coronary artery calcium (CAC), as automatically quantified on routinely performed computed tomography scans, are associated with cardiovascular and coronary artery diseases.

Major finding: The risk for cardiovascular disease increased with a higher CAC score (adjusted hazard ratio, 1.8, 2.1, and 3.4 for CAC scores 11-100, 101-400, and greater than 400, respectively). The risk for coronary artery disease also increased with an increase in CAC score (adjusted hazard ratio, 2.8, 4.3, and 7.8 for CAC scores 11-100, 101-400, and greater than 400, respectively).

Study details: A multicenter cohort study of 15,915 patients with breast cancer who received radiotherapy between 2005 and 2016. The CAC scores were automatically extracted from computed tomography scans using a deep learning algorithm.

Disclosure: This study was funded by the Dutch Cancer Society. The authors received grants, lecture fees, and research support from various sources. Dr. Leiner and Dr. Isgum owned shares of Quantib-U BV and/or a patent with royalties planned. No other conflicts of interest were reported.

Source: Gal R et al. JAMA Oncol. 2021 May 6. doi: 10.1001/jamaoncol.2021.1144.

Key clinical point: The presence and extent of coronary artery calcium (CAC), as automatically quantified on routinely performed computed tomography scans, are associated with cardiovascular and coronary artery diseases.

Major finding: The risk for cardiovascular disease increased with a higher CAC score (adjusted hazard ratio, 1.8, 2.1, and 3.4 for CAC scores 11-100, 101-400, and greater than 400, respectively). The risk for coronary artery disease also increased with an increase in CAC score (adjusted hazard ratio, 2.8, 4.3, and 7.8 for CAC scores 11-100, 101-400, and greater than 400, respectively).

Study details: A multicenter cohort study of 15,915 patients with breast cancer who received radiotherapy between 2005 and 2016. The CAC scores were automatically extracted from computed tomography scans using a deep learning algorithm.

Disclosure: This study was funded by the Dutch Cancer Society. The authors received grants, lecture fees, and research support from various sources. Dr. Leiner and Dr. Isgum owned shares of Quantib-U BV and/or a patent with royalties planned. No other conflicts of interest were reported.

Source: Gal R et al. JAMA Oncol. 2021 May 6. doi: 10.1001/jamaoncol.2021.1144.

Key clinical point: Breast-conserving surgery (BCS) with radiotherapy yields superior survival vs. mastectomy in patients with early-stage breast cancer.

Major finding: At a median follow-up of 6.28 years, mastectomy without radiotherapy vs. BCS with radiotherapy was associated with worse overall survival (OS; hazard ratio [HR], 1.79; P less than .001) and breast cancer-specific survival (BCSS; HR, 1.66; P less than .001). Mastectomy with radiotherapy also showed lower OS (HR, 1.24; P less than .001) and BCSS (HR, 1.28; P=.001) vs. BCS and radiotherapy.

Study details: A cohort study of 48,986 patients with primary invasive T1-2 N0-2 breast cancer who underwent breast surgery between 2008 and 2017.

Disclosure: This work was funded by the Swedish Breast Cancer Association. Dr de Boniface was supported by an investigator award from the Swedish Cancer Society, and Ms Johansson was supported by a research grant from the Swedish Research Council. The authors did not declare any conflict of interest.

Source: de Boniface J et al. JAMA Surg. 2021 May 5. doi: 10.1001/jamasurg.2021.1438.

Key clinical point: Breast-conserving surgery (BCS) with radiotherapy yields superior survival vs. mastectomy in patients with early-stage breast cancer.

Major finding: At a median follow-up of 6.28 years, mastectomy without radiotherapy vs. BCS with radiotherapy was associated with worse overall survival (OS; hazard ratio [HR], 1.79; P less than .001) and breast cancer-specific survival (BCSS; HR, 1.66; P less than .001). Mastectomy with radiotherapy also showed lower OS (HR, 1.24; P less than .001) and BCSS (HR, 1.28; P=.001) vs. BCS and radiotherapy.

Study details: A cohort study of 48,986 patients with primary invasive T1-2 N0-2 breast cancer who underwent breast surgery between 2008 and 2017.

Disclosure: This work was funded by the Swedish Breast Cancer Association. Dr de Boniface was supported by an investigator award from the Swedish Cancer Society, and Ms Johansson was supported by a research grant from the Swedish Research Council. The authors did not declare any conflict of interest.

Source: de Boniface J et al. JAMA Surg. 2021 May 5. doi: 10.1001/jamasurg.2021.1438.

Key clinical point: Breast-conserving surgery (BCS) with radiotherapy yields superior survival vs. mastectomy in patients with early-stage breast cancer.

Major finding: At a median follow-up of 6.28 years, mastectomy without radiotherapy vs. BCS with radiotherapy was associated with worse overall survival (OS; hazard ratio [HR], 1.79; P less than .001) and breast cancer-specific survival (BCSS; HR, 1.66; P less than .001). Mastectomy with radiotherapy also showed lower OS (HR, 1.24; P less than .001) and BCSS (HR, 1.28; P=.001) vs. BCS and radiotherapy.

Study details: A cohort study of 48,986 patients with primary invasive T1-2 N0-2 breast cancer who underwent breast surgery between 2008 and 2017.

Disclosure: This work was funded by the Swedish Breast Cancer Association. Dr de Boniface was supported by an investigator award from the Swedish Cancer Society, and Ms Johansson was supported by a research grant from the Swedish Research Council. The authors did not declare any conflict of interest.

Source: de Boniface J et al. JAMA Surg. 2021 May 5. doi: 10.1001/jamasurg.2021.1438.

Adjuvant T-DM1 is recommended for patients with HER2-positive early breast cancer with residual disease after neoadjuvant therapy based on phase 3 results. The KATHERINE study found a significant reduction for the risk of recurrence and death with adjuvant T-DM1 vs trastuzumab. Subgroup analyses from KATHERINE showed similar benefits with T-DM1 irrespective of type of neoadjuvant regimen. Furthermore, T-DM1 appeared to benefit small node-negative tumors and particularly those tumors considered high-risk (Mamounas). In the phase 3 TRAIN-2 study, similar pCR rates (68% vs 67%), as well as 3 year event-free (94% vs 93%) and overall (98% vs 98%) survival, were observed for non-anthracycline and anthracycline-containing regimens. These findings highlight the broad applicability of T-DM1 in the adjuvant setting, the rationale to support de-escalation and omission of anthracyclines for HER2-positive tumors, and the importance of tailoring therapy based on response.

Brain metastases occur in up to 50% of patients with HER2-positive metastatic breast cancer (MBC). Effective therapies for this population represent an unmet clinical need. The phase 2 PATRICIA study demonstrated activity of pertuzumab plus high-dose trastuzumab (6mg/kg weekly) for patients with HER2-positive MBC and central nervous system (CNS) progression after radiotherapy. In 37 patients evaluable for efficacy, the CNS objective response rate was 11%, clinical benefit rate at 4 and 6 months was 68% and 51%, respectively, and 2 patients had stable disease for over 2 years (Lin). Data supports the role of other HER2-targeted therapies for CNS disease including T-DM1, neratinib, and tucatinib. Among 291 patients with brain metastases in HER2CLIMB, the combination of tucatinib, capecitabine, and trastuzumab improved median overall survival (18 vs 12 months) and CNS progression-free survival (9.9 vs 4.2 months), compared with capecitabine plus trastuzumab. Further investigation exploring other novel therapy combinations and biomarkers will help further improve outcomes for these patients.

Adjuvant endocrine therapy decreases the risk for recurrence and improves survival for women diagnosed with HR-positive breast cancer. For young women, endocrine therapy options include tamoxifen, as well as ovarian suppression plus tamoxifen, or an aromatase inhibitor. Recommended duration of therapy is at least 5 years and can extend to 10 years. These treatments and duration may present challenges related to childbearing attempts and raise fertility concerns among young women.  In the Young Women’s Breast Cancer Study, among 643 women aged 40 years or younger and diagnosed with early stage HR-positive breast cancer, one-third reported fertility concerns impacting endocrine therapy decisions. Those who reported fertility concerns were more likely to exhibit non-initiation or non-persistence to endocrine therapy (40% vs 20%). Among women with fertility concerns, 7% did not initiate endocrine therapy, and 33% were non-persistent over 5 years (Sella). It is essential to integrate early oncofertility dialogue to help achieve optimal endocrine therapy and address family planning goals.

Studies have shown sugar-sweetened beverages (SSB) increase the risk for insulin resistance, diabetes, and heart disease. In a subsample of Women’s Health Initiative participants, higher levels of insulin resistance were shown to be linked to an increased incidence of breast cancer and all-cause mortality after breast cancer. Researchers found that among 8,863 women diagnosed with early breast cancer, those who consumed SSB after diagnosis had higher breast cancer-specific mortality and all-cause mortality. Additionally, replacing SSB with coffee, tea or water was linked to a decrease in mortality (Farvid). These findings support discussion of lifestyle and dietary behaviors in the survivorship setting, as these modifiable risk factors can potentially have significant health implications.

References:

van der Voort A, van Ramshorst MS, van Werkhoven ED, et al. Three-year follow-up of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2-blockade for HER2-positive breast cancer (TRAIN-2): A randomized phase III trial. J Clin Oncol. 2020;38S:ASCO #501.

Lin NU, Borges V, Anders C, et al. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol. 2020;38(23):2610-2619.

Pan K, Chlebowski RT, Mortimer JE, et al. Insulin resistance and breast cancer incidence and mortality in postmenopausal women in the Women's Health Initiative. Cancer. 2020;126(16):3638-3647.

Adjuvant T-DM1 is recommended for patients with HER2-positive early breast cancer with residual disease after neoadjuvant therapy based on phase 3 results. The KATHERINE study found a significant reduction for the risk of recurrence and death with adjuvant T-DM1 vs trastuzumab. Subgroup analyses from KATHERINE showed similar benefits with T-DM1 irrespective of type of neoadjuvant regimen. Furthermore, T-DM1 appeared to benefit small node-negative tumors and particularly those tumors considered high-risk (Mamounas). In the phase 3 TRAIN-2 study, similar pCR rates (68% vs 67%), as well as 3 year event-free (94% vs 93%) and overall (98% vs 98%) survival, were observed for non-anthracycline and anthracycline-containing regimens. These findings highlight the broad applicability of T-DM1 in the adjuvant setting, the rationale to support de-escalation and omission of anthracyclines for HER2-positive tumors, and the importance of tailoring therapy based on response.

Brain metastases occur in up to 50% of patients with HER2-positive metastatic breast cancer (MBC). Effective therapies for this population represent an unmet clinical need. The phase 2 PATRICIA study demonstrated activity of pertuzumab plus high-dose trastuzumab (6mg/kg weekly) for patients with HER2-positive MBC and central nervous system (CNS) progression after radiotherapy. In 37 patients evaluable for efficacy, the CNS objective response rate was 11%, clinical benefit rate at 4 and 6 months was 68% and 51%, respectively, and 2 patients had stable disease for over 2 years (Lin). Data supports the role of other HER2-targeted therapies for CNS disease including T-DM1, neratinib, and tucatinib. Among 291 patients with brain metastases in HER2CLIMB, the combination of tucatinib, capecitabine, and trastuzumab improved median overall survival (18 vs 12 months) and CNS progression-free survival (9.9 vs 4.2 months), compared with capecitabine plus trastuzumab. Further investigation exploring other novel therapy combinations and biomarkers will help further improve outcomes for these patients.

Adjuvant endocrine therapy decreases the risk for recurrence and improves survival for women diagnosed with HR-positive breast cancer. For young women, endocrine therapy options include tamoxifen, as well as ovarian suppression plus tamoxifen, or an aromatase inhibitor. Recommended duration of therapy is at least 5 years and can extend to 10 years. These treatments and duration may present challenges related to childbearing attempts and raise fertility concerns among young women.  In the Young Women’s Breast Cancer Study, among 643 women aged 40 years or younger and diagnosed with early stage HR-positive breast cancer, one-third reported fertility concerns impacting endocrine therapy decisions. Those who reported fertility concerns were more likely to exhibit non-initiation or non-persistence to endocrine therapy (40% vs 20%). Among women with fertility concerns, 7% did not initiate endocrine therapy, and 33% were non-persistent over 5 years (Sella). It is essential to integrate early oncofertility dialogue to help achieve optimal endocrine therapy and address family planning goals.

Studies have shown sugar-sweetened beverages (SSB) increase the risk for insulin resistance, diabetes, and heart disease. In a subsample of Women’s Health Initiative participants, higher levels of insulin resistance were shown to be linked to an increased incidence of breast cancer and all-cause mortality after breast cancer. Researchers found that among 8,863 women diagnosed with early breast cancer, those who consumed SSB after diagnosis had higher breast cancer-specific mortality and all-cause mortality. Additionally, replacing SSB with coffee, tea or water was linked to a decrease in mortality (Farvid). These findings support discussion of lifestyle and dietary behaviors in the survivorship setting, as these modifiable risk factors can potentially have significant health implications.

References:

van der Voort A, van Ramshorst MS, van Werkhoven ED, et al. Three-year follow-up of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2-blockade for HER2-positive breast cancer (TRAIN-2): A randomized phase III trial. J Clin Oncol. 2020;38S:ASCO #501.

Lin NU, Borges V, Anders C, et al. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol. 2020;38(23):2610-2619.

Pan K, Chlebowski RT, Mortimer JE, et al. Insulin resistance and breast cancer incidence and mortality in postmenopausal women in the Women's Health Initiative. Cancer. 2020;126(16):3638-3647.

Adjuvant T-DM1 is recommended for patients with HER2-positive early breast cancer with residual disease after neoadjuvant therapy based on phase 3 results. The KATHERINE study found a significant reduction for the risk of recurrence and death with adjuvant T-DM1 vs trastuzumab. Subgroup analyses from KATHERINE showed similar benefits with T-DM1 irrespective of type of neoadjuvant regimen. Furthermore, T-DM1 appeared to benefit small node-negative tumors and particularly those tumors considered high-risk (Mamounas). In the phase 3 TRAIN-2 study, similar pCR rates (68% vs 67%), as well as 3 year event-free (94% vs 93%) and overall (98% vs 98%) survival, were observed for non-anthracycline and anthracycline-containing regimens. These findings highlight the broad applicability of T-DM1 in the adjuvant setting, the rationale to support de-escalation and omission of anthracyclines for HER2-positive tumors, and the importance of tailoring therapy based on response.

Brain metastases occur in up to 50% of patients with HER2-positive metastatic breast cancer (MBC). Effective therapies for this population represent an unmet clinical need. The phase 2 PATRICIA study demonstrated activity of pertuzumab plus high-dose trastuzumab (6mg/kg weekly) for patients with HER2-positive MBC and central nervous system (CNS) progression after radiotherapy. In 37 patients evaluable for efficacy, the CNS objective response rate was 11%, clinical benefit rate at 4 and 6 months was 68% and 51%, respectively, and 2 patients had stable disease for over 2 years (Lin). Data supports the role of other HER2-targeted therapies for CNS disease including T-DM1, neratinib, and tucatinib. Among 291 patients with brain metastases in HER2CLIMB, the combination of tucatinib, capecitabine, and trastuzumab improved median overall survival (18 vs 12 months) and CNS progression-free survival (9.9 vs 4.2 months), compared with capecitabine plus trastuzumab. Further investigation exploring other novel therapy combinations and biomarkers will help further improve outcomes for these patients.

Adjuvant endocrine therapy decreases the risk for recurrence and improves survival for women diagnosed with HR-positive breast cancer. For young women, endocrine therapy options include tamoxifen, as well as ovarian suppression plus tamoxifen, or an aromatase inhibitor. Recommended duration of therapy is at least 5 years and can extend to 10 years. These treatments and duration may present challenges related to childbearing attempts and raise fertility concerns among young women.  In the Young Women’s Breast Cancer Study, among 643 women aged 40 years or younger and diagnosed with early stage HR-positive breast cancer, one-third reported fertility concerns impacting endocrine therapy decisions. Those who reported fertility concerns were more likely to exhibit non-initiation or non-persistence to endocrine therapy (40% vs 20%). Among women with fertility concerns, 7% did not initiate endocrine therapy, and 33% were non-persistent over 5 years (Sella). It is essential to integrate early oncofertility dialogue to help achieve optimal endocrine therapy and address family planning goals.

Studies have shown sugar-sweetened beverages (SSB) increase the risk for insulin resistance, diabetes, and heart disease. In a subsample of Women’s Health Initiative participants, higher levels of insulin resistance were shown to be linked to an increased incidence of breast cancer and all-cause mortality after breast cancer. Researchers found that among 8,863 women diagnosed with early breast cancer, those who consumed SSB after diagnosis had higher breast cancer-specific mortality and all-cause mortality. Additionally, replacing SSB with coffee, tea or water was linked to a decrease in mortality (Farvid). These findings support discussion of lifestyle and dietary behaviors in the survivorship setting, as these modifiable risk factors can potentially have significant health implications.

References:

van der Voort A, van Ramshorst MS, van Werkhoven ED, et al. Three-year follow-up of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2-blockade for HER2-positive breast cancer (TRAIN-2): A randomized phase III trial. J Clin Oncol. 2020;38S:ASCO #501.

Lin NU, Borges V, Anders C, et al. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol. 2020;38(23):2610-2619.

Pan K, Chlebowski RT, Mortimer JE, et al. Insulin resistance and breast cancer incidence and mortality in postmenopausal women in the Women's Health Initiative. Cancer. 2020;126(16):3638-3647.

In the study, 60 patients were classified as having EPI based on the gold standard test of PABA excretion, then the FBHC of the two groups were compared. According to the study findings FBHC levels were higher in the EPI group 15.70 (1.4 to 77.0) ppm than in the non-PEI group 2.80 (0.7 to 28.2) ppm (P < 0.0001).  The cutoff value for FBHC of 10.7 ppm (95% CI: 0.678–0.913; P < 0.001) showed a sensitivity of 73.3% and a specificity of 83.3% for PEI diagnosis. Interestingly, to prove biologic plausibility, the researchers also looked at microbiome analysis and found that there was a significant increase of relative abundance of phylum Firmicutes (P < 0.05) and the genus Clostridium (P < 0.05) in the EPI group. The researchers suggested that the flow of undigested food in EPI may select for Clorstridia species, which are the main hydrogen producing bacteria in the intestine. 

In AZN Journal of Surgery, Chan-Min Choi, et al looked at management of palliative stage pancreatic ductal adenocarcinomas (PDAC)  in 67 patients with locally advanced or metastatic pancreatic cancer at Western Health in Melbourne.² Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively, and median body mass index decreased by 13.3% from pre-illness to cancer diagnosis. Yet, despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. The researchers concluded that the "study shows a lack of clear guideline for diagnosis and management of EPI for palliative PDAC.”

Finally a study by Johnston et al. in Gastroenterology looked at predictors of exocrine pancreatic insufficiency in 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45).³ EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The researchers looked at predictors of EPI including variables such as preoperative A1c, smoking status, neoadjuvant chemo and radio therapy, and age, among others. In the final multivariate analysis, the only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% CI, 0.88-0.98; P < 0.01). While these studies may not immediately change practice, they offer further steps in the direction towards better diagnostics and more appropriate management of EPI.  

References 

1. Uetsuki K, Kawashima H, Ohno E, et al. Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency. BMC Gastroenterol 2021;21(1):211.

2. Choi CC-M, Choi J, Houli N, et al. Evaluation of palliative treatments in unresectable pancreatic cancer. ANZ J Surg 2021;

3. Johnston ME, Wahab SA, Turner K, et al. 298 post-pancreatectomy volumetric analysis: a missing variable in the development of post-operative endocrine and exocrine dysfunction. Gastroenterology 2021;160(6):S-878.

In the study, 60 patients were classified as having EPI based on the gold standard test of PABA excretion, then the FBHC of the two groups were compared. According to the study findings FBHC levels were higher in the EPI group 15.70 (1.4 to 77.0) ppm than in the non-PEI group 2.80 (0.7 to 28.2) ppm (P < 0.0001).  The cutoff value for FBHC of 10.7 ppm (95% CI: 0.678–0.913; P < 0.001) showed a sensitivity of 73.3% and a specificity of 83.3% for PEI diagnosis. Interestingly, to prove biologic plausibility, the researchers also looked at microbiome analysis and found that there was a significant increase of relative abundance of phylum Firmicutes (P < 0.05) and the genus Clostridium (P < 0.05) in the EPI group. The researchers suggested that the flow of undigested food in EPI may select for Clorstridia species, which are the main hydrogen producing bacteria in the intestine. 

In AZN Journal of Surgery, Chan-Min Choi, et al looked at management of palliative stage pancreatic ductal adenocarcinomas (PDAC)  in 67 patients with locally advanced or metastatic pancreatic cancer at Western Health in Melbourne.² Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively, and median body mass index decreased by 13.3% from pre-illness to cancer diagnosis. Yet, despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. The researchers concluded that the "study shows a lack of clear guideline for diagnosis and management of EPI for palliative PDAC.”

Finally a study by Johnston et al. in Gastroenterology looked at predictors of exocrine pancreatic insufficiency in 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45).³ EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The researchers looked at predictors of EPI including variables such as preoperative A1c, smoking status, neoadjuvant chemo and radio therapy, and age, among others. In the final multivariate analysis, the only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% CI, 0.88-0.98; P < 0.01). While these studies may not immediately change practice, they offer further steps in the direction towards better diagnostics and more appropriate management of EPI.  

References 

1. Uetsuki K, Kawashima H, Ohno E, et al. Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency. BMC Gastroenterol 2021;21(1):211.

2. Choi CC-M, Choi J, Houli N, et al. Evaluation of palliative treatments in unresectable pancreatic cancer. ANZ J Surg 2021;

3. Johnston ME, Wahab SA, Turner K, et al. 298 post-pancreatectomy volumetric analysis: a missing variable in the development of post-operative endocrine and exocrine dysfunction. Gastroenterology 2021;160(6):S-878.

In the study, 60 patients were classified as having EPI based on the gold standard test of PABA excretion, then the FBHC of the two groups were compared. According to the study findings FBHC levels were higher in the EPI group 15.70 (1.4 to 77.0) ppm than in the non-PEI group 2.80 (0.7 to 28.2) ppm (P < 0.0001).  The cutoff value for FBHC of 10.7 ppm (95% CI: 0.678–0.913; P < 0.001) showed a sensitivity of 73.3% and a specificity of 83.3% for PEI diagnosis. Interestingly, to prove biologic plausibility, the researchers also looked at microbiome analysis and found that there was a significant increase of relative abundance of phylum Firmicutes (P < 0.05) and the genus Clostridium (P < 0.05) in the EPI group. The researchers suggested that the flow of undigested food in EPI may select for Clorstridia species, which are the main hydrogen producing bacteria in the intestine. 

In AZN Journal of Surgery, Chan-Min Choi, et al looked at management of palliative stage pancreatic ductal adenocarcinomas (PDAC)  in 67 patients with locally advanced or metastatic pancreatic cancer at Western Health in Melbourne.² Weight loss and steatorrhea were present in 83.6% and 13.4% of patients, respectively, and median body mass index decreased by 13.3% from pre-illness to cancer diagnosis. Yet, despite high rates of referral to dieticians (79.1%), only 24 patients were prescribed pancreatic enzyme replacement therapy. The researchers concluded that the "study shows a lack of clear guideline for diagnosis and management of EPI for palliative PDAC.”

Finally a study by Johnston et al. in Gastroenterology looked at predictors of exocrine pancreatic insufficiency in 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45).³ EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The researchers looked at predictors of EPI including variables such as preoperative A1c, smoking status, neoadjuvant chemo and radio therapy, and age, among others. In the final multivariate analysis, the only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% CI, 0.88-0.98; P < 0.01). While these studies may not immediately change practice, they offer further steps in the direction towards better diagnostics and more appropriate management of EPI.  

References 

1. Uetsuki K, Kawashima H, Ohno E, et al. Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency. BMC Gastroenterol 2021;21(1):211.

2. Choi CC-M, Choi J, Houli N, et al. Evaluation of palliative treatments in unresectable pancreatic cancer. ANZ J Surg 2021;

3. Johnston ME, Wahab SA, Turner K, et al. 298 post-pancreatectomy volumetric analysis: a missing variable in the development of post-operative endocrine and exocrine dysfunction. Gastroenterology 2021;160(6):S-878.

Key clinical point: Patients with chronic pancreatitis, pancreatic cancer, and pancreatic resection, followed-up by a gastroenterologist had higher rates of screening for exocrine pancreatic insufficiency (EPI) and appropriate prescription of pancreatic enzyme replacement therapy (PERT).

Major finding: EPI screening by measurement of pancreatic elastase (odds ratio [OR], 5.94; P less than .001), PERT prescription (OR, 2.02; P less than .001), and prescription for a minimally effective dosage (OR, 1.5; P = .008) was higher in patients followed-up by gastroenterologist (n=470) vs. those who were not (n=994).

Study details: This retrospective study assessed 1,464 patients with either EPI, chronic pancreatitis, pancreatic cancer, or pancreatic resection at the University of Florida between February 2018 and February 2020.

Disclosures: No source of funding was identified.

Source: Ladna M et al. Gastroenterology. 2021 May 10. doi: 10.1016/S0016-5085(21)01015-5.

Key clinical point: Patients with chronic pancreatitis, pancreatic cancer, and pancreatic resection, followed-up by a gastroenterologist had higher rates of screening for exocrine pancreatic insufficiency (EPI) and appropriate prescription of pancreatic enzyme replacement therapy (PERT).

Major finding: EPI screening by measurement of pancreatic elastase (odds ratio [OR], 5.94; P less than .001), PERT prescription (OR, 2.02; P less than .001), and prescription for a minimally effective dosage (OR, 1.5; P = .008) was higher in patients followed-up by gastroenterologist (n=470) vs. those who were not (n=994).

Study details: This retrospective study assessed 1,464 patients with either EPI, chronic pancreatitis, pancreatic cancer, or pancreatic resection at the University of Florida between February 2018 and February 2020.

Disclosures: No source of funding was identified.

Source: Ladna M et al. Gastroenterology. 2021 May 10. doi: 10.1016/S0016-5085(21)01015-5.

Key clinical point: Patients with chronic pancreatitis, pancreatic cancer, and pancreatic resection, followed-up by a gastroenterologist had higher rates of screening for exocrine pancreatic insufficiency (EPI) and appropriate prescription of pancreatic enzyme replacement therapy (PERT).

Major finding: EPI screening by measurement of pancreatic elastase (odds ratio [OR], 5.94; P less than .001), PERT prescription (OR, 2.02; P less than .001), and prescription for a minimally effective dosage (OR, 1.5; P = .008) was higher in patients followed-up by gastroenterologist (n=470) vs. those who were not (n=994).

Study details: This retrospective study assessed 1,464 patients with either EPI, chronic pancreatitis, pancreatic cancer, or pancreatic resection at the University of Florida between February 2018 and February 2020.

Disclosures: No source of funding was identified.

Source: Ladna M et al. Gastroenterology. 2021 May 10. doi: 10.1016/S0016-5085(21)01015-5.

Key clinical point: Postoperative pancreas remnant volume was associated with the development of exocrine pancreatic insufficiency (EPI) after pancreatic resection.

Major finding: EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The incidence of EPI was higher in patients receiving Whipple vs. distal pancreatectomy (66% vs. 21%; P = .004). The only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% confidence interval, 0.88-0.98; P less than .01).

Study details: This study included 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45) at a single institution between 2017 and 2018.

Disclosures: No source of funding was identified.

Source: Johnston ME et al. Gastroenterology. 2021 May 10. doi: 10.1016/S0016-5085(21)02827-4.

Key clinical point: Postoperative pancreas remnant volume was associated with the development of exocrine pancreatic insufficiency (EPI) after pancreatic resection.

Major finding: EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The incidence of EPI was higher in patients receiving Whipple vs. distal pancreatectomy (66% vs. 21%; P = .004). The only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% confidence interval, 0.88-0.98; P less than .01).

Study details: This study included 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45) at a single institution between 2017 and 2018.

Disclosures: No source of funding was identified.

Source: Johnston ME et al. Gastroenterology. 2021 May 10. doi: 10.1016/S0016-5085(21)02827-4.

Key clinical point: Postoperative pancreas remnant volume was associated with the development of exocrine pancreatic insufficiency (EPI) after pancreatic resection.

Major finding: EPI, requiring pancreatic enzyme replacement therapy, developed in 50% of patients at 1-year postpancreatectomy. The incidence of EPI was higher in patients receiving Whipple vs. distal pancreatectomy (66% vs. 21%; P = .004). The only factor associated with EPI development was postoperative remnant pancreas volume (odds ratio, 0.93; 95% confidence interval, 0.88-0.98; P less than .01).

Study details: This study included 68 patients who underwent pancreatectomy (distal, n=23; pancreaticoduodenectomy, n=45) at a single institution between 2017 and 2018.

Disclosures: No source of funding was identified.

Source: Johnston ME et al. Gastroenterology. 2021 May 10. doi: 10.1016/S0016-5085(21)02827-4.

Key clinical point: Considerable proportion of patients suffer from exocrine pancreatic insufficiency (EPI)-associated complaints which persisted for 3 years or even more after pancreatoduodenectomy or left pancreatectomy, even in patients receiving pancreatic enzyme replacement therapy (PERT).

Major finding: EPI, indicated by PERT usage, was reported in 41% of patients, of which only 48% reported complete relief, whereas 35% reported decrease in EPI-related complaints. Patients with vs. without PERT had higher complaints of fatty stools (50% vs. 26%; P = .003) and unintentional weight loss (11% vs. 2%; P = .019).

Study details: This study included 153 patients who underwent pancreatoduodenectomy or left pancreatectomy for premalignant or benign diseases between 2006 and 2016.

Disclosures: This study was supported by the Dutch Cancer Society. The lead author reported research funding from Mylan and Allergan.

Source: Latenstein AEJ et al. HPB. 2021 Apr 27. doi: 10.1016/j.hpb.2021.04.012.

Key clinical point: Considerable proportion of patients suffer from exocrine pancreatic insufficiency (EPI)-associated complaints which persisted for 3 years or even more after pancreatoduodenectomy or left pancreatectomy, even in patients receiving pancreatic enzyme replacement therapy (PERT).

Major finding: EPI, indicated by PERT usage, was reported in 41% of patients, of which only 48% reported complete relief, whereas 35% reported decrease in EPI-related complaints. Patients with vs. without PERT had higher complaints of fatty stools (50% vs. 26%; P = .003) and unintentional weight loss (11% vs. 2%; P = .019).

Study details: This study included 153 patients who underwent pancreatoduodenectomy or left pancreatectomy for premalignant or benign diseases between 2006 and 2016.

Disclosures: This study was supported by the Dutch Cancer Society. The lead author reported research funding from Mylan and Allergan.

Source: Latenstein AEJ et al. HPB. 2021 Apr 27. doi: 10.1016/j.hpb.2021.04.012.

Key clinical point: Considerable proportion of patients suffer from exocrine pancreatic insufficiency (EPI)-associated complaints which persisted for 3 years or even more after pancreatoduodenectomy or left pancreatectomy, even in patients receiving pancreatic enzyme replacement therapy (PERT).

Major finding: EPI, indicated by PERT usage, was reported in 41% of patients, of which only 48% reported complete relief, whereas 35% reported decrease in EPI-related complaints. Patients with vs. without PERT had higher complaints of fatty stools (50% vs. 26%; P = .003) and unintentional weight loss (11% vs. 2%; P = .019).

Study details: This study included 153 patients who underwent pancreatoduodenectomy or left pancreatectomy for premalignant or benign diseases between 2006 and 2016.

Disclosures: This study was supported by the Dutch Cancer Society. The lead author reported research funding from Mylan and Allergan.

Source: Latenstein AEJ et al. HPB. 2021 Apr 27. doi: 10.1016/j.hpb.2021.04.012.