Erin Roesch, MD
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.