Clinical Edge Journal Scan

Clinical Edge Journal Scan Commentary: Breast Cancer May 2021

Dr. Roesch scans the journals, so you don't have to!

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Erin Roesch, MD

Sacituzumab govitecan (SG) is an antibody-drug conjugate directed at Trop-2 which is highly expressed in breast cancer. The randomized phase 3 ASCENT trial compared SG to treatment of physician’s choice (TCP) (eribulin, vinorelbine, capecitabine or gemcitabine) among patients with relapsed or refractory metastatic TNBC who had received at least two prior lines of therapy including a taxane. SG demonstrated improvement in progression-free survival (PFS) and overall survival (OS) compared to TPC (PFS 5.6 months versus 1.7 months, HR 0.41, p<0.001; median OS 12.1 months versus 6.7 months, HR 0.48, p<0.001), as well higher response rates (objective response 35% versus 5%) . SG is also being evaluated in different settings (neoadjuvant, adjuvant) and breast cancer subtypes. The phase 3 TROPiCS-02 trial is evaluating SG versus TPC in HR+/HER2-negative metastatic breast cancer, based on encouraging results from a subset of patients (who had progressed on endocrine therapy and received at least one prior line of chemotherapy) enrolled on a phase I/II basket trial showing an objective response rate of 31.5%, median PFS of 5.5 months and median OS of 12 months.

Potential advantages of a neoadjuvant systemic therapy approach including downstaging of the primary breast tumor and axilla, as well the ability to assess tumor response which can have prognostic and adjuvant therapy implications. Samiei and colleagues performed a systematic review and meta-analysis of 33 studies (57,531 patients) in the neoadjuvant setting to assess axillary pathologic complete response (pCR) rates among clinically node-positive breast cancer of various subtypes. HR-negative/HER2-positive subtype was associated with the highest pCR rate (60%) followed by 59% for HER2-positive, 48% for triple-negative, 45% for HR+/HER2-positive, 35% for luminal B, 18% for HR+/HER2-negative, and 13% for luminal A . Achievement of axillary pCR after pre-operative chemotherapy has been associated with improvement in relapse-free survival and overall survival. Furthermore, this data stimulates consideration of less invasive axillary staging in certain patients pending chemotherapy response, and the contribution of breast cancer subtype and impact on outcomes deserves further investigation.

Chemotherapy-induced alopecia (CIA) during breast cancer treatment can affect an individual’s perception of their own appearance, body image, overall health and therefore may impact quality of life. Wang et al performed a meta-analysis including 27 studies with 2,202 participants and demonstrated a 61% effectiveness rate of scalp cooling to protect hair loss. The effectiveness rates of scalp cooling when taxanes and anthracyclines were used alone were higher compared to combination therapy (74% for taxanes, 66% for anthracyclines, and 54% for combination). A prospective study including 139 patients treated with anthracycline chemotherapy for breast cancer receiving scalp cooling found a 43% success rate (hair loss £50%). It is important to consider chemotherapy regimen, side effects (headache, dizziness, pain, nausea), resources and cost when counseling patients regarding scalp cooling. Future studies exploring ways to address these potential challenges will be beneficial to improve patient access and tolerance to scalp cooling.

Obesity is associated with increased risk of various types of cancers, and can have a detrimental effect on cancer prognosis as well as treatment response and tolerance. Potential mechanisms to explain the relationship between obesity, physical activity and breast cancer prognosis include increased levels of sex and metabolic hormones, alteration in adipokine levels, and increased inflammation, oxidative stress and angiogenesis. A retrospective cohort study including 6,481 patients with an initial non-metastatic breast cancer diagnosis, majority of whom were overweight (33.4%) or obese (33.8%), observed increasing BMI (for every 5 kg/m 2 BMI increase) was associated with an increased risk of second cancer development (7%, RR=1.07; p=0.01), obesity-related cancer (13%, RR=1.13; p<0.001), second breast cancer (11%, RR=1.11; p0.01) and second ER-positive breast cancer (15%, RR1.15; p0.008). There are several ongoing clinical trials that are examining the impact of diet and weight loss interventions on breast cancer outcomes (DIANA-5, B-AHEAD3, Breast Cancer Weight Loss Study). These studies will be key to counseling and empowering patients to address potentially modifiable variables that can positively impact their health.

References:

Kalinsky K, Diamond JR, Vahdat LT, Tolaney SM, Juric D, O’Shaughnessy J, Moroose RL, Mayer IA, Abramson VG, Goldengerg DM, Sharkey RM, Maliakel P, Hong Q, Goswami T, Wegener WA, Bardia A. Sacituzumab govitecan in previously treated hormone receptor-positive/ HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial. Ann Oncol. 2020;31:1709-1718.

Mougalian SS, Hernandez M, Lei X, Lynch S, Kuerer HM, Symmans WF, Theriault RL, Fornage BD, Hsu L, Buchholz TA, Sahin AA, Hunt KK, Yang WT, Hortobagyi GN, Valero V. Ten-year outcomes of patients with breast cancer with cytologically confirmed axillary lymph node metastases and pathologic complete response after primary systemic chemotherapy. JAMA Oncol . 2016;2:508-516.

Munzone M, Bagnardi V, Campennì G, Mazzocco K, Pagan E, Tramacere A, Masiero M, Iorfida M, Mazza M, Montagna E, Cancello G, Bianco N, Palazzo A, Cardillo A, Dellapasqua S, Sangalli C, Pettini G, Pravettoni G, Colleoni M, Veronesi P. Preventing chemotherapy-induced alopecia: a prospective clinical trial on the efficacy and safety of a scalp-cooling system in early breast cancer patients treated with anthracyclines. Br J Cancer. 2019;121:325–331.

McTiernan A. Weight, physical activity and breast cancer survival. Proc Nutr Soc. 2018;77:403–411.

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