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Simple Summary: Abemaciclib is an important addition to the care of women with hormone receptor-positive breast cancer. To qualify for abemaciclib treatment, some women are advised to undergo axillary node clearance surgery as finding more than three axillary nodes with metastatic cancer allows access to abemaciclib. This paper explores the balance between the benefits of axillary node clearance in permitting access to abemaciclib and the harms of surgery. We examine how many women need to undergo axillary node clearance before one woman clinically benefits from the procedure. We show that for every 10 women undergoing axillary node clearance surgery, only one eventually qualifies for abemaciclib. The remaining nine would have axillary surgery but still not qualify for abemaciclib as less than four metastatic axillary nodes are found despite full axillary clearance. However, these women could still suffer the complications of axillary node clearance surgery. The monarchE study added the CDK4/6 inhibitor abemaciclib to the care of women with oestrogen-positive (ER+) breast cancers. Eligibility required meeting monarchE criteria—either >3 positive axillary nodes, or 1–3 positive sentinel nodes (SNB+) with tumour size >50 mm or grade 3 cancers. Women were advised to proceed to completion axillary node clearance (cANC) if size/grade criteria were not fulfilled for >3 positive nodes to be identified. However, cANC is associated with significant morbidity, conflicting with the potential benefits of abemaciclib. We analysed data of 229 consecutive women (2016-2022) with ER+ breast cancer and SNB+ who proceeded to cANC, keeping with contemporary treatment guidelines. We used this cohort to assess numbers that, under national guidance in place currently, would be advised to undergo cANC solely to check eligibility for abemaciclib treatment. Using monarchE criteria, 90 women (39%) would have accessed abemaciclib based on SNB+ and size/grade, without cANC. In total, 139 women would have been advised to proceed to cANC to check eligibility, with only 15/139 (11%) having >3 positive nodes after sentinel node biopsy and cANC. The remaining 124 (89%) would have undergone cANC but remained ineligible for abemaciclib. Size, age, grade, and Ki67 did not predict >3 nodes at cANC. Following cANC, a large majority of women with ER+, <50 mm, and grade 1–2 tumours remain ineligible for abemaciclib yet are subject to significant morbidity including lifelong lymphoedema risk. The monarchE authors state that 15 women need abemaciclib therapy for 1 to clinically benefit. Thus, in our cohort, 139 women undergoing cANC would lead to one woman benefitting. [ABSTRACT FROM AUTHOR]

Simple Summary: This study reports the management of women at high risk for breast cancer over a 33 years period. The aim was to summarize the numbers seen and to report the results of our studies on gene testing, the outcomes of screening and the success of preventive methods including lifestyle change, chemoprevention and risk-reducing mastectomy. We also discuss how the clinical Family History Service may be improved in the future. Clinics for women concerned about their family history of breast cancer are widely established. A Family History Clinic was set-up in Manchester, UK, in 1987 in a Breast Unit serving a population of 1.8 million. In this review, we report the outcome of risk assessment, screening and prevention strategies in the clinic and propose future approaches. Between 1987–2020, 14,311 women were referred, of whom 6.4% were from known gene families, 38.2% were at high risk (≥30% lifetime risk), 37.7% at moderate risk (17–29%), and 17.7% at an average/population risk who were discharged. A total of 4168 (29.1%) women were eligible for genetic testing and 736 carried pathogenic variants, predominantly in BRCA1 and BRCA2 but also other genes (5.1% of direct referrals). All women at high or moderate risk were offered annual mammographic screening between ages 30 and 40 years old: 646 cancers were detected in women at high and moderate risk (5.5%) with a detection rate of 5 per 1000 screens. Incident breast cancers were largely of good prognosis and resulted in a predicted survival advantage. All high/moderate-risk women were offered lifestyle prevention advice and 14–27% entered various lifestyle studies. From 1992–2003, women were offered entry into IBIS-I (tamoxifen) and IBIS-II (anastrozole) trials (12.5% of invitees joined). The NICE guidelines ratified the use of tamoxifen and raloxifene (2013) and subsequently anastrozole (2017) for prevention; 10.8% women took up the offer of such treatment between 2013–2020. Since 1994, 7164 eligible women at ≥25% lifetime risk of breast cancer were offered a discussion of risk-reducing breast surgery and 451 (6.2%) had surgery. New approaches in all aspects of the service are needed to build on these results. [ABSTRACT FROM AUTHOR]