Current State of the Art in the Adjuvant Systemic Treatment of Premenopausal Patients With Early Breast Cancer

Abstract

Breast cancer is the most frequent malignancy diagnosed in premenopausal women. In this age group, breast tumors tend to be diagnosed at more advanced stages and to harbor more aggressive biological features. In addition, specific age-related issues including genetic counseling, fertility preservation, impact on social and couple relationships, working life, and management of long-term side effects should be considered highly relevant when managing early breast cancer in premenopausal women. Therefore, the care of these patients is particularly complex and a multidisciplinary approach is mandatory. The present review summarizes the current state of art in the adjuvant systemic treatment of premenopausal women with early breast cancer focusing on the optimal chemotherapy, endocrine therapy, and targeted therapy approaches in this specific patient population.

Ovarian Function Suppression With Luteinizing Hormone-Releasing Hormone Agonists for the Treatment of Hormone Receptor-Positive Early Breast Cancer in Premenopausal Women

“…In premenopausal breast cancer patients with aggressive TNBC, treatment options are limited, and prognosis is poor relative to patients with HR+ cancers. In these patients, whose tumors are resistant to endocrine therapy and HER2-targeting treatments, cytotoxic chemotherapy remains the only well-validated and approved treatment in the adjuvant setting following surgery ( 16 ); although the development of immune checkpoint inhibitors, including programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1), is changing the treatment landscape for these patients ( 17 ).…”

“…In HR−/HER2-positive (HER2+) patients, the anti-HER2 agent trastuzumab has transformed disease outcomes and has become the standard of care given as a monotherapy or in combination with other drugs including paclitaxel ( 16 ). Newer agents, including pertuzumab ( 18 ), trastuzumab emtansine ( 19 ), and neratinib ( 20 ), have also shown effectiveness in the treatment of patients with HER2+ tumors.…”

“…Premenopausal women diagnosed with early breast cancer associated with unfavorable clinico-pathological features are candidates for treatment with systemic chemotherapy. In this group of patients, adjuvant chemotherapy has demonstrated clinical effectiveness in reducing risk of breast cancer relapse and death ( 16 ). However, in these, typically younger, women there is a risk of long-lasting and impactful toxicities associated with chemotherapy.…”

Gender-specific aspects related to type of fertility preservation strategies and access to fertility care

“…111 Prior concerns for breast cancer patients with hormone receptor-positive disease on a potential detrimental antagonism between chemotherapy and an endocrine agent have been recently dispelled with the observation of similar survival outcomes between patients receiving systemic cytotoxic therapy with or without concurrent LHRHa. 111 118 In these patients, considering the known prognostic value of chemotherapy-induced amenorrhea and the role of ovarian function suppression, [119][120][121] prolonging treatment with LHRHa up to 5 years should be considered as part of adjuvant endocrine therapy. 109 110 122 CONCLUSIONS Having a family after prior cancer diagnosis and treatment completion is feasible but timing is crucial.…”

Patient experiences and views on pharmaceutical care during adjuvant endocrine therapy for breast cancer: A qualitative study

“…Between 4% and 30% of women with hormone receptor (HR)‐positive breast cancer who completed primary treatment of early‐stage breast cancer (EBC) do not initiate the follow‐up long‐term adjuvant endocrine therapy (AET) (Berkowitz et al, 2021 ; Kroenke et al, 2018 ; Neugut et al, 2012 ; O'Neill et al, 2017 ), and 15–43% are non‐adherent (i.e., do not take medication as prescribed) (Berkowitz et al, 2021 ; Cavazza et al, 2020 ; Font et al, 2019 ; Lailler et al, 2021 ; Lambert‐Côté et al, 2020 ; Makubate et al, 2013 ; Mislang et al, 2017 ; Murphy et al, 2012 ). AET is used in patients with oestrogen receptor (ER)‐positive EBC for at least 5 years in order to prevent recurrence and reduce the mortality (Cardoso et al, 2019 ; Early Breast Cancer Trialists' Collaborative Group, 2011 ) and comprises the (sequential) use of the selective ER modulator (SERM) tamoxifen and aromatase inhibitors (AIs) like anastrozole, exemestane and letrozole (Burstein et al, 2019 ; Cardoso et al, 2019 ; Parisi et al, 2020 ). AET non‐adherence has been associated with increased risks of recurrence and mortality (Barron et al, 2013 ; Chirgwin et al, 2016 ; Font et al, 2019 ; Hershman et al, 2011 ; Inotai et al, 2021 ; Lee et al, 2019 ; Makubate et al, 2013 ; Mislang et al, 2017 ; Winn & Dusetzina, 2016 ) and higher healthcare costs resulting from more physician visits, increased hospitalisation rates and longer hospital stays (McCowan et al, 2013 ; Mislang et al, 2017 ).…”