|Year : 2021 | Volume
| Issue : 1 | Page : 35-37
Advances in breast cancer research in 2020: changes in clinical practice
GA Toshib, Suhani
Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India
|Date of Submission||25-Dec-2020|
|Date of Decision||31-Dec-2020|
|Date of Acceptance||06-Jan-2021|
|Date of Web Publication||24-Mar-2021|
Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Toshib G A, Suhani. Advances in breast cancer research in 2020: changes in clinical practice. Indian J Cancer 2021;58:35-7
The year 2020 will go down in history as one of the most testing times for healthcare institutions worldwide due to the COVID-19 pandemic. This has forced global medical facilities to prioritize their resources for the management and mitigation of the pandemic. This however must not divert our concerns about other serious health issues in the forefront, like breast cancer. Hence, we review some of the key advances in breast cancer research in 2020 (including a related publication from 2019).
A triple algorithmic approach of i) preoperative resource optimization by prioritizing and fast-tracking patient visits of symptomatic new visits suspicious for malignancy and promoting single visit for a rapid diagnosis and treatment planning; ii) ensuring surgical safety with preoperative COVID-19 risk stratification and testing, reducing interdepartmental contact, and adhering to operating theatre safety protocols; and iii) promoting team-based care and enhanced patient communication to facilitate timely patient discharge, patient education of self-care, “virtual” multidisciplinary discussion, and open relay of information to patient. Such adaptations have helped clinicians in the real world to help deliver breast care services worldwide.
HER2/neu positive breast cancers are considered as one of the poor prognostic breast cancers and trials have been underway for managing this subtype. In the management of patients with progressive metastatic breast cancer who have been treated with trastuzumab, pertuzumab, and trastuzumab emtansine, adding tucatinib to capecitabine and trastuzumab resulted in improved progression-free survival (PFS) (33.1% at 1 year vis-à-vis 10% for placebo combination arm) and overall survival at 2 years (44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group) in the HER2CLIMB trial. There was a modest improvement in median duration of progression-free survival (7.8 and 5.6 months, respectively) with a higher incidence of diarrhea and elevated liver enzymes in tucatinib arm. The drug has been approved by the United States Food and Drug Administration (US FDA) on April 17, 2020 for use in metastatic breast cancer previously treated by at least one anti-HER2/neu-based regimens. On December 20, 2019, US FDA announced an accelerated approval for trastuzumab deruxtecan, another drug active against HER2/neu positive breast cancers. The DESTINY-Breast01 trial evaluated the role of trastuzumab deruxtecan in adults with pathologically documented HER2/neu positive metastatic breast cancer previously treated with transtuzumab emtansine. Typically, 60.9% person women showed response to drug in the intention to treat analysis. The median response duration was 14.8 months (95% confidence interval = 13.8–16.9) with a progression-free survival of 16.4 months. However, the side effect profile was unfavorable with interstitial lung disease developing in 13.6% of the patients. Larger randomized clinical trials to assess its efficacy and side-effect profile are pending.
The absence of any molecular or hormonal receptor target for triple negative breast cancer (TNBC) coupled with their occurrence in a relatively younger age group and poor prognosis has made the management of this subset of tumors a challenge. The KEYNOTE-522 trial showed some hope in these tumors and reported that addition of pembrolizumab to chemotherapy (paclitaxel + carboplatin) for previously untreated early stage TNBC (stage II, III) resulted in significantly higher pathological complete response rates. The evidence as of now is however not strong enough to suggest that pathological complete response translates to an improved survival rate.
Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to the active metabolite of irinotecan, SN-38, via a unique hydrolyzable linker that allows for SN-38 release intracellularly and in the tumor microenvironment (bystander effect). In a phase I/II IMMU-132-01 study, SG demonstrated 33% objective response rate and an median PFS of 5.5 months in patients with metastatic TNBC with manageable safety, leading to accelerated US FDA approval of SG. In the ASCENT study presented at the European Society of Medical Oncology Virtual Congress 2020, patients with metastatic TNBC who had relapsed/refractory disease after ≥2 prior chemotherapies (prior taxane required) were randomized 1:1 to receive SG (10 mg/kg intravenous on day 1, 8 every 21 days) or single-agent TPC (treatment of physician's choice) (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. The trial demonstrated significant improvement in the progression-free survival and overall survival in the SG arm.
While the hormone-receptor-positive cancers are considered to be having better prognosis, the estimation of proliferation index (Ki67) has helped in the identification of tumors having a worse outcome in this subgroup. The POETIC (Peri-Operative Endocrine Therapy—Individualizing Care) trial was designed to test whether short duration presurgical endocrine therapy in postmenopausal women with estrogen receptor positive early breast cancer improved the clinical outcomes. It also had an objective of identifying patients with good prognosis by studying the change in Ki67 index to triage poor prognostic patients who should be considered for additional therapies such as chemotherapy. The study concluded that giving perioperative endocrine therapy with aromatase inhibitor had no significant effect on long-term oncological outcome and that using baseline Ki67 as well as Ki67 post 2 weeks of endocrine therapy could help guide adjuvant treatment, by considering additional modalities such as chemotherapy for those with a higher post therapy Ki67 index.
Trials studying clinical utility of ribociclib have been published, viz. CORALLEEN and MONALEESA-3 trials. The CORALLEEN trial assessed the biological and clinical activity of neoadjuvant ribociclib plus letrozole in the luminal B subtype of early stage breast cancer (stage I-III). MONALEESA-3 trial showed a significant overall survival benefit by adding ribociclib to fulvestrant in patients with hormone-receptor-positive, HER2/neu-negative advanced breast cancer.
The patients with BRCA mutation carriers pose another therapeutic challenge as they are many times triple negative affecting women with younger age and often tend to have a worse prognosis. Neoadjuvant single-agent oral talazoparib (without chemotherapy) given once per day for 6 months to HER2/neu-negative operable breast cancer patients with germline pathogenic BRCA variant produced patholigcal complete response rate of 53% (sample size of study = 20) with manageable toxicity. The results of the phase 1/2 MEDIOLA trial demonstrated that the combination of olaparib and durvalumab had promising anti-tumor activity and safety in patients with pathogenic BRCA mutation. The results BROCADE3 trial suggested that addition of veliparib to carboplatin, with continuation as monotherapy if the platinum doublet were discontinued, resulted in significant and durable improvement in progression-free survival in patients with germline BRCA mutation-associated HER2/neu-negative advanced breast cancer. Further trails are however still needed for better understanding of the efficacy and adverse reaction profiles of these drugs.
Adjuvant local radiotherapy after primary surgery for early-stage breast cancer is often prescribed. The FAST-FORWARD trial demonstrated that 26 Gy in five fractions is noninferior to the standard of 40 Gy in 15 fractions over 3 weeks for local tumor control and is safe in terms of normal tissue effects up to 5 years in such a subgroup. The 1-week schedule has major benefits over the 3-week or 5-week regimens in terms of convenience and cost for patients. In this COVID-19 pandemic, the 1-week schedule appears more relevant and feasible leading to lesser number of hospital visits for the patients. Also, in resource limited countries wherein the availability of functioning radiotherapy units is scarce, the abbreviated radiotherapy regimen will make the services available to greater number of patients.
Breast cancer screening is a commonplace in the west, and screen-detected cancers are shown to be of early stage. In a cohort of 69,025 women aged between 50 and 64 years who participated in population-based breast cancer screening program, 206 interval breast cancers were diagnosed. These interval breast cancers were more likely to be estrogen-negative, have a high tumor grade as well as breast cancer specific mortality as compared to the screen detected breast cancers.
This article was peer-reviewed internally.
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Conflicts of interest
There are no conflicts of interest.
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