Antibody–drug conjugates (ADCs) are revolutionizing cancer treatment, adding another important new class of systemic therapy. ADCs are a specially designed class of therapeutics that target cells expressing specific cancer antigens using directed antibody–drug delivery and release a cytotoxic chemotherapeutic payload. Over the past two decades, improvements in ADC design, development, and research, particularly in breast cancer, have led to several recent landmark publications. These advances have significantly changed various treatment paradigms and revamped traditional classifications of breast cancer with the introduction of a potential new subtype: “HER2-low”. This review will focus on several ADCs developed for breast cancer treatment, including trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG) and other newer emerging agents. It will provide an overview of the role of ADCs in breast cancer and discuss the opportunities and challenges they present. Additionally, our review will discuss future research directions to improve the selection of targets, combination therapies, and aim to improve drug safety. Important first-line metastatic and adjuvant clinical trials are underway, which may expand the role of ADC therapy in breast cancer. We foresee ADCs driving a new era of breast cancer treatment, adding to the steady incremental survival advantage observed in recent years.

Background: Anthracycline-taxane is the standard chemotherapy strategy for treating high-risk early breast cancer despite the potentially life-threatening adverse events caused by anthracyclines. Commonly, the combination of docetaxel and cyclophosphamide (TC) is considered an alternative option. However, the efficacy of TC compared to anthracycline-taxane chemotherapy is unclear. This study compares disease-free survival (DFS), overall survival (OS) and cardiotoxicity between adjuvant TC and anthracycline-taxane for stages I–III, HER2-negative breast cancer. Methods: A systematic search on MEDLINE, Embase and Cochrane CENTRAL for randomized-controlled trials published until 11 March 2024, yielded 203 studies with 11,803 patients, and seven trials were included. Results: TC results in little to no difference in DFS (HR 1.09, 95% CI 0.98–1.20; moderate-certainty of evidence); OS (1.02, 95% CI 0.89–1.16; high-certainty of evidence); and cardiotoxicity (RR 0.54, 95% CI 0.16–1.76; high-certainty of evidence), compared to anthracycline-taxane. In the subgroup analysis, patients with ≥4 lymph nodes had improved DFS from anthracycline-taxane over TC. Conclusions: Overall, there was no difference between TC and anthracycline-taxane in DFS, OS and cardiotoxicity. In women with ≥4 nodes, anthracycline-taxane was associated with a substantial reduction in relapse events, compared to TC. Our study supports the current standard of practice, which is to use anthracycline-taxane and TC chemotherapy as a reasonable option in select cases.

Background: Approximately 75% of breast cancer (BC) is associated with luminal differentiation expressing endocrine receptors (ER). For ER+ HER2− tumors, adjuvant endocrine therapy (ET) is the cornerstone treatment. Although relapse events steadily continue, the ET benefits translate to dramatically lengthen life expectancy with bearable side-effects. This review of ER+ HER2− female BC outlines suitable adjuvant treatment strategies to help guide clinical decision making around appropriate therapy. Methods: A literature search was conducted in Embase, Medline, and the Cochrane Libraries, using ER+ HER−, ET BC keywords. Results: In low-risk patients: five years of ET is the standard option. While Tamoxifen remains the preferred selection for premenopausal women, AI is the choice for postmenopausal patients. In the high-risk category: ET plus/minus OFS with two years of Abemaciclib is recommended. Although extended ET for a total of ten years is an alternative, the optimal AI duration is undetermined; nevertheless an additional two to three years beyond the initial five years may be sufficient. In this postmenopausal group, bisphosphonate is endorsed. Conclusions: Classifying the risk category assists in deciding the treatment route and its optimal duration. Tailoring the breadth of ET hinges on a wide array of factors to be appraised for each individualized case, including weighing its benefits and harms.

Background: The overexpression of the human epidermal growth factor receptor 2 (HER2+) accounts for 15–20% of all breast cancer phenotypes. Even after the completion of the standard combination of chemotherapy and trastuzumab, relapse events occur in approximately 15% of cases. The neoadjuvant approach has multiple benefits that include the potential to downgrade staging and convert previously unresectable tumors to operable tumors. In addition, achieving a pathologic complete response (pCR) following preoperative systemic treatment is prognostic of enhanced survival outcomes. Thus, optimal evaluation among the suitable strategies is crucial in deciding which patients should be selected for the neoadjuvant approach. Methods: A literature search was conducted in the Embase, Medline, and Cochrane electronic libraries. Conclusion: The evaluation of tumor and LN staging and, hence, stratifying BC recurrence risk are decisive factors in guiding clinicians to optimize treatment decisions between the neoadjuvant versus adjuvant approaches. For each individual case, it is important to consider the most likely postsurgical outcome, since, if the patient does not obtain pCR following neoadjuvant treatment, they are eligible for adjuvant T-DM1 in the case of residual disease. This review of HER2-positive female BC outlines suitable neoadjuvant and adjuvant systemic treatment strategies for guiding clinical decision making around the selection of an appropriate therapy.

Purpose of review: To provide an overview of the recent advancements in predicting toxicity associated with cancer treatment in older patients. Recent findings: Various screening tools and validated risk calculators have been shown to help predict toxicity from surgery and chemotherapy. Radiation therapy has been more challenging to select the appropriate tool to reliably predict patients at risk for toxicity and noncompliance. Ongoing work on electronic geriatric assessment tools is showing promise in making comprehensive assessment more feasible. Summary: Selecting appropriate cancer therapy is particularly important in older patients, and validated tools have been developed to guide clinicians for surgery and chemotherapy; however, radiotherapy toxicity remains an area for further development, as does the uptake of existing tools into routine oncology practice.

Background: Anthracycline–taxane chemotherapy is the gold standard in high-risk breast cancer (BC), despite the potential risk of congestive heart failure (CHF). A suitable alternative for anthracycline-sparing chemotherapy is through the combination of docetaxel and cyclophosphamide (TC). Methods: Through a retrospective study of stage I-III HER2-negative BC, using administrative databases, we analyzed a total of 10,634 women treated with adjuvant chemotherapy in Ontario, Canada, between 2009 and 2017. We compared TC versus standardized anthracycline–taxane chemotherapies (ACT and FEC-D). We investigated the overall survival (OS), and explored the incidence of CHF, emergency department (ED) visits and febrile neutropenia. Results: With a median follow-up of 5.5 years, the 5-year analysis showed an increased OS in patients treated with TC, versus those treated with ACT, HR 0.77 (0.63–0.95, p = 0.015). Among ER+ BC, there was an increased OS in patients treated with ACT and FEC-D, versus those treated with TC, HR 0.70 (0.52–0.95, p = 0.021) and HR 0.71 (0.56–0.91, p = 0.007), respectively. There were no substantial differences in CHF, between TC and anthracycline-based treatments. Patients treated with TC and FEC-D had more ED visits, compared to those treated with ACT. Conclusion: Our study shows that anthracycline–taxane regimens were the most commonly prescribed adjuvant chemotherapy options in HER2-negative BC. Women who received ACT had the lowest OS, likely due to their unfavorable pathology.