The Role of Ki67 in Evaluating Neoadjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer

Ki67 is a proliferation marker. It has been proposed as a useful clinical marker for breast cancer subtype classification, prognosis, and prediction of therapeutic response. But the questionable analytical validity of Ki67 prevents its widespread adoption of these measures for treatment decisions in breast cancer. Currently, Ki67 has been tested as a predictive marker for chemotherapy using clinical and pathological response as endpoints in neoadjuvant endocrine therapy. Ki67 can be used as a predictor to evaluate the recurrence-free survival rate of patients, or its change can be used to predict the preoperative “window of opportunity” in neoadjuvant endocrine therapy. In this review, we will elaborate on the role of Ki67 in neoadjuvant endocrine therapy in breast cancer.

Innovative Standards in Surgery of the Breast after Neoadjuvant Systemic Therapy

<b><i>Background:</i></b> The goal of neoadjuvant systemic therapy (NST) in breast cancer is to downstage tumors and downgrade treatment. Indications are constantly evolving. These changes raise practical questions for planning of surgery after NST. <b><i>Summary:</i></b> In this review we discuss current evolving aspects of surgery of the breast after NST. Breast-conserving surgery (BCS) eligibility increases after NST – both neoadjuvant chemotherapy (NAC) and neoadjuvant endocrine therapy. Adequate margin width in NST and upfront surgery are similar – “no tumor on ink” for invasive cancer. Oncoplastic breast surgery after NST is feasible – both for BCS and mastectomy with reconstruction. There is increasing interest in the possibility of omitting surgery in patients with a complete response to NAC. Several trials are being conducted in aim of achieving acceptable prediction of pathological complete response, by combination of imaging and percutaneous biopsy of the tumor bed, as well as assessing the safety of such an approach. <b><i>Key Messages:</i></b> Surgery of the breast after NST should be determined not only according to biologic and anatomic parameters at diagnosis, but is dynamic, and must be tailored according to the response to therapy. The omission of surgery in exceptional responders after NAC is being explored.

Axillary Lymph Node Dissection Rates and Prognosis From Phase III Neoadjuvant Systemic Trial Comparing Neoadjuvant Chemotherapy With Neoadjuvant Endocrine Therapy in Pre-Menopausal Patients With Estrogen Receptor-Positive and HER2-Negative, Lymph Node-Positive Breast Cancer

In this study, we aimed to evaluate axillary lymph node dissection (ALND) rates and prognosis in neoadjuvant chemotherapy (NCT) compare with neoadjuvant endocrine therapy (NET) in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), lymph node (LN)-positive, premenopausal breast cancer patients (NCT01622361). The multicenter, phase 3, randomized clinical trial enrolled 187 women from July 5, 2012, to May 30, 2017. The patients were randomly assigned (1:1) to either 24 weeks of NCT including adriamycin plus cyclophosphamide followed by intravenous docetaxel, or NET involving goserelin acetate and daily tamoxifen. ALND was performed based on the surgeon’s decision. The primary endpoint was ALND rate and surgical outcome after preoperative treatment. The secondary endpoint was long-term survival. Among the 187 randomized patients, pre- and post- neoadjuvant systemic therapy (NST) assessments were available for 170 patients. After NST, 49.4% of NCT patients and 55.4% of NET patients underwent mastectomy after treatment completion. The rate of ALND was significantly lower in the NCT group than in the NET group (55.2% vs. 69.9%, P=.046). Following surgery, the NET group showed a significantly higher mean number of removed LNs (14.96 vs. 11.74, P=.003) and positive LNs (4.84 vs. 2.92, P=.000) than the NCT group. The axillary pathologic complete response (pCR) rate was significantly higher in the NCT group (13.8% vs. 4.8%, P=.045) than in the NET group. During a median follow-up of 67.3 months, 19 patients in the NCT group and 12 patients in the NET group reported recurrence. The 5-year ARFS (97.5%vs. 100%, P=.077), DFS (77.2% vs. 84.8%, P=.166), and OS (97.5% vs. 94.7%, P=.304) rates did not differ significantly between the groups. In conclusion, although survival did not differ significantly, more NCT patients might able to avoid ALND, with fewer LNs removed with lower LN positivity.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT01622361, identifier NCT01622361.

Bridging Endocrine Therapy for HR+/HER2- Resectable Breast Cancer: Is it Safe?

Background The COVID-19 pandemic has required new treatment paradigms to limit exposures and optimize hospital resources, including the use of neoadjuvant endocrine therapy (NAET) as bridging therapy for HR+/HER2-invasive tumors and DCIS. While this approach has been used in locally advanced disease, it is unclear how it may affect outcomes in resectable HR+/HER2- tumors. Methods Women ≥18 years diagnosed with in situ (Tis) or non-metastatic HR+/HER2- breast cancer from March-May 2019 and 2020 were included. Fisher’s exact test and two-sample t test were used to compare baseline characteristics and surgical outcomes between strata. Sub-analysis was performed between patients who received primary surgery vs a bridging NAET approach. Results Despite similar clinical characteristics, patients in 2019 were more likely to have a surgery-first approach (75% vs 42%, P-value = .0007), receive surgery sooner (22 vs 29 days, P-value < .001), and within 60 days from diagnosis date (100% vs 85%, P-value = .0301). Neoadjuvant endocrine therapy was a more prevalent approach in 2020 (48% vs 7%, P-value < .0001). Rates of clinical to pathologic up-staging remained consistent across primary surgery vs bridging NAET subgroups ( P-value = .9253). Discussion Pandemic-driven treatment protocols provide a unique opportunity to assess the utility of bridging endocrine therapy for resectable HR+/HER2- tumors. Differences in clinical and pathologic staging were similar across groups and did not appear to be affected by receipt of NAET. Our limited cohort demonstrates this strategic therapeutic avenue can optimize health care utilization and may be a reasonable approach when delaying surgery is preferred.