Despite being a standard treatment option in breast cancer, immune checkpoint inhibitors (ICIs) are only efficacious for a subset of patients. To gain a better understanding of the antitumor immune response in breast cancer, we examined the heterogeneity of CD8 ⁺ T cells in tumors, metastatic lymph nodes (mLNs), and peripheral blood from patients with early breast cancer ( n = 131). Among tissue-resident memory CD8 ⁺ T (T _RM ) cells, including virus- and tumor-specific CD8 ⁺ T cells, CD39 expression was observed in a tumor-specific and exhausted subpopulation in both tumors and mLNs. CD39 ⁺ T _RM cells from tumors and mLNs exhibited a phenotypic similarity and clonally overlapped with each other. Moreover, tumor or mLN CD39 ⁺ T _RM cells clonally overlapped with CD39 ⁻ T _RM and non-T _RM cells in the same compartment, implying a tissue-specific differentiation process. These inter-subpopulationally overlapping CD39 ⁺ T _RM clonotypes were frequently detected among effector memory CD8 ⁺ T cells in peripheral blood, suggesting a systemic clonal overlap. CD39 ⁺ T _RM cell enrichment was heterogeneous among molecular subtypes of breast cancer, which is associated with the different role of antitumor immune responses in each subtype. In vitro blockade of PD-1 and/or CTLA-4 effectively restored proliferation of CD39 ⁺ T _RM cells and enhanced cytokine production by CD8 ⁺ T cells from tumors or mLNs, particularly in the presence of CD39 ⁺ T _RM enrichment. This suggests that CD39 ⁺ T _RM cells have a capacity for functional restoration upon ICI treatment. Thus, our study indicates that CD39 ⁺ T _RM cells with a clonal overlap across compartments are key players in antitumor immunity in breast cancer.

PURPOSE: The nodal burden of patients with residual isolated tumor cells (ITCs) in the sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) (ypN0i+) is unknown, and axillary management is not standardized. We investigated rates of additional positive lymph nodes (LNs) at axillary lymph node dissection (ALND) and oncologic outcomes in patients with ypN0i+ treated with and without ALND. METHODS: The Oncoplastic Breast Consortium-05/ICARO cohort study (ClinicalTrials.gov identifier: NCT06464341 ) retrospectively analyzed data from patients with stage I to III breast cancer with ITCs in SLNs after NAC from 62 centers in 18 countries. The primary end point was the 3-year rate of any axillary recurrence. The rate of any invasive recurrence was the secondary end point. RESULTS: In total, 583 patients were included, of whom 182 (31%) had completion ALND and 401 (69%) did not. The median age was 48 years. Most patients (74%) were clinically node-positive at diagnosis and 41% had hormone receptor–positive/human epidermal growth factor receptor 2–negative tumors. The mean number of SLNs with ITCs was 1.2. Patients treated with ALND were more likely to present with cN2/3 disease (17% v 7%, P < .001), have ITCs detected on frozen section (62% v 8%, P < .001), have lymphovascular invasion (38% v 24%, P < .001), and receive adjuvant chest wall (89% v 78%, P = .024) and nodal radiation (82% v 75%, P = .038). Additional positive nodes were found at ALND in 30% of patients, but only 5% had macrometastases. The 3-year rates of any axillary and any invasive recurrence were 2% (95% CI, 0.95 to 3.6) and 11% (95% CI, 8 to 14), respectively, with no statistical difference by type of axillary surgery. CONCLUSION: The nodal burden in patients with ypN0(i+) was low, and axillary recurrence after ALND omission was rare in patients selected for this approach. These results do not support routine ALND in all patients with ypN0(i+).

Kim HS, et al. J Breast Cancer. 2019 Jul;22:e35. https://doi.org/10.4048/jbc.2019.22.e35

Jung JJ, et al. J Breast Cancer. 2024 Feb;27:e8. https://doi.org/10.4048/jbc.2023.0265

Background: Hormone replacement therapy (HRT) increases the risk of breast cancer, but the association may vary according to patient factors. We investigated the association between HRT and breast cancer in a nationwide cohort with risk stratification according to risk factors for breast cancer. Methods: Using the Korean National Health Insurance Service database, 4,558,376 postmenopausal women who underwent breast cancer screening and regular health checkups from 2009 to 2014 were analyzed. Results: A total of 696,084 (15.3%) women reported current or previous HRT use. Breast cancer was newly diagnosed in 26,797 (0.6%) women during a median follow-up of 5.35 years. The HR of the risk of breast cancer in HRT users was 1.25 [95% confidence interval (CI), 1.22–1.29] compared with HRT nonusers. The risk of breast cancer increased according to HRT duration [adjusted HR = 1.08; 95% CI, 1.04–1.12, for <2 years; adjusted HR = 1.33; 95% CI, 1.25–1.40, for 2 to <5 years; and adjusted HR = 1.72; 95% CI, 1.63–1.82, for ≥5 years). The effects of HRT on breast cancer risk applied to both invasive and in situ cancer. The HRT-related risk of breast cancer was higher in women who were leaner and those who had dense breasts. Conclusions: This nationwide population-based study confirms the association between HRT use and breast cancer risk. The risk increased proportionally with duration of HRT and differed according to body weight and breast density. Impacts: Risk stratification would be useful when deciding whether to apply HRT for relief of menopausal symptoms.

Kang YJ, et al. J Breast Cancer. 2021 Dec;24:e55. https://doi.org/10.4048/jbc.2021.24.e55