A Rosier Picture for Young Women With Breast Cancer
Authors: Ellen Warner
Journal: Journal of Clinical Oncology (2016)

Women who are diagnosed with breast cancer before age 35 or 40 years represent a small proportion of patients in the developed world with breast cancer; however, these patients contribute disproportionately to breast cancer mortality—with a lower survival rate andmore life-years lost per patient death—and they bear a disproportionate burden of the physical and psychological morbidity of the diagnosis and its treatments. Higher local, regional, and distant recurrence rates observed in young women with breast cancer (YWBC) are a function of the later disease stage at presentation as a result of the absence of population screening for this age group, diagnostic delays, and more rapidly proliferating tumors, and of a worse prognosis for any given stage because of more aggressive biology. Compared with breast cancers in older women, these tumors have a greater frequency of adverse morphologic and molecular features, such as high grade, lymphovascular invasion, human epidermal growth factor receptor 2 (HER2) overexpression, absence of hormone receptors, and a triple-negative biomarker profile. Some investigators have found young age to be an independent, adverse prognostic factor even after correcting for these other characteristics, whereas others have not. It has been suggested that patients who express the hormone receptor (HR)–positive/HER2-negative subtype may be the only subgroup of YWBC who have an intrinsically worse prognosis than that of older women because of a greater ratio of luminal B to luminal A cancers. For the oncologist who treats YWBC, finding the optimal balance between minimizing the risk of cancer recurrence and maximizing long-term quality of life can be a major challenge. The appropriateness of breast-conserving therapy (BCT) for YWBC has become a controversial subject, given the significantly higher incidence of recurrence in the breast of YWBC and the fact that few YWBC were enrolled in the large randomized trials that demonstrated equivalent survival after mastectomy or BCT. The worry about local undertreatment with BCT was magnified by results from the Early Breast Cancer Trialists’ Collaborative Group, which found that local treatments that prevented in-breast cancer recurrence were associated with a lower risk of death after 15 years. Accordingly, in 2005 the National Comprehensive Cancer Network recommended that age , 35 years be considered an indication for mastectomy. Although this guideline has since been modified, as recently as 2013 the majority of the St Gallen International Breast Cancer Expert Panel considered age , 35 years to be a relative contraindication to BCT. Several recent studies have settled this debate with the finding that, despite a higher local recurrence rate for YWBC after BCT compared with mastectomy, survival is equivalent. Yet, when deciding the type of surgery to undergo, survival is not the only important issue to consider for YWBC. Although BCT has obvious psychological benefits, many young patients wish to minimize the psychological trauma and morbidity of local cancer recurrence and its treatment. Regarding the latter, in addition to the desire to avoid further treatment with chemotherapy, many YWBC do not want to risk undergoing a future mastectomy that has more limited reconstruction options as a result of their previous breast radiation. The rising proportion of YWBCwho are at a low objective risk for contralateral breast cancer yet opt for bilateral mastectomy is further evidence that decisions by this group about breast surgery, in part, are driven by peace of mind rather than survival considerations. Rates of local recurrence (LR) are decreasing in YWBC. Adjuvant systemic therapy and a radiation boost to the tumor bed have each been shown to decrease LR in young patients by approximately 50%. In counseling a young woman who is uncertain about which type of surgery to choose, it would be helpful to be able to accurately estimate her risk of LR with contemporary treatment, and, ideally, to take into account her specific tumor features. In the article that accompanies this editorial, Aalders et al report the 5-year local, regional, and distant recurrence rates for a cohort of 1,000 women with nonmetastatic breast cancer who were diagnosed at age# 35 years, between 2003 and 2008, and whowere initially treated with surgery. These women represented 2% of patients with breast cancer who were enrolled in the Netherlands Cancer Registry during that period. Results are stratified by biomarker subtype, on the basis of HR andHER2 status, and by year of diagnosis. Of patients, 95% were stage 1 or 2, and 45% underwent BCT. Throughout the study period, . 90% of patients received chemotherapy, . 95% of HR-positive patients received hormonal therapy, and all patients who were treated with BCT received a boost dose of radiation to the tumor bed. In 2005, however, treatment with trastuzumab became the standard of care for the HER-positive patients. The overall 5-year risk of in-breast recurrence after BCT was 3.2%, and the risk of chest wall recurrence after mastectomy was 3.8%, which amounted to an overall risk of LR of 3.5%. LR rate