HER2-low status may predict poor neoadjuvant chemotherapy response in HR-negative breast cancer: a real-world multicenter study.

OBJECTIVE: We aimed to investigate the impact of human epidermal growth factor receptor 2 status (human epidermal growth factor receptor 2-low versus human epidermal growth factor receptor 2-zero) on pathological response to neoadjuvant chemotherapy and survival outcomes in early-stage breast cancer. METHODS: Patients with primary invasive breast cancer received neoadjuvant chemotherapy between July 2018 and July 2021 were identified from six hospitals. The primary efficacy end-point was total pathological complete response. The second short-term efficacy end-points include breast pathological complete response, axillary lymph nodes pathological complete response and the score of Miller-Payne grade. Long-term efficacy end-point was disease-free survival. RESULTS: 429 patients with human epidermal growth factor receptor 2 negative invasive tumors were included, 267 (62.24%) had human epidermal growth factor receptor 2-low tumors. Hormone receptor-positive patients had a higher percentage of human epidermal growth factor receptor 2-low tumors compared to hormone receptor-negative patients (71.97% versus 42.14%). The pathological response rate was significantly lower in human epidermal growth factor receptor 2-low tumors than in human epidermal growth factor receptor 2-zero tumors for total patients in univariate analysis, including the rates of total pathological complete response (5.2% versus 14.2%), breast pathological complete response (6.4% versus 17.3%), nodes pathological complete response (26.3% versus 37.7%) and MP4-5 (21.2% versus 33.8%). Subgroup analysis showed that the rates of total pathological complete response, breast pathological complete response and MP4-5 were also significantly lower in human epidermal growth factor receptor 2-low tumors versus human epidermal growth factor receptor 2-zero tumors in both univariate and multivariate analysis in hormone receptor-negative subgroup. With the median follow-up of 24 months, disease-free survival was comparable between these two subgroups (P = 0.816). CONCLUSIONS: Our results demonstrate that human epidermal growth factor receptor 2-low tumors achieved a significantly lower pathological complete response rate with conventional chemotherapy than those with human epidermal growth factor receptor 2-zero tumors, especially for hormone receptor-negative group. Large, randomized, prospective studies are needed to confirm our data and further evaluate the prognostic value of human epidermal growth factor receptor 2-low expression.

Axilla View of Mammography in Preoperative Axillary Lymph Node Evaluation of Breast Cancer Patients: A Pilot Study.

PURPOSE: This study aimed to explore a novel position of mammography named axilla view in axillary lymph node (ALN) evaluation in breast cancer. PATIENTS AND METHODS: Patients were prospectively enrolled and scheduled for mammography before surgery. Investigated imaging patterns included mediolateral oblique (2D-MLO) and axilla view (2D-axilla) of mammography, and axilla view of digital breast tomosynthesis (3D-axilla). The correlation of ALN numbers between imaging and pathology was analyzed. Diagnostic performance was analyzed via AUC. RESULTS: 75 patients were included. A larger and clearer axillary region was displayed in axilla view. The total number of ALNs detected under 2D/3D-axilla view was significantly higher than that under 2D-MLO view (4.6 vs. 2.5, P < .001; 5.6 vs. 4.6, P = .034). Correlations between number of positive ALNs detected under 2D/3D-axilla view and pathologically confirmed metastatic ALNs were stronger than 2D-MLO view (Pearson correlation coefficients: 0.7084,0.7044 and 0.4744). The proportion of cases with ≥5 positive ALNs detected under 3D-axilla view was significantly higher than that under 2D-MLO (38.2% vs. 14.7%, P = .028). The overweight and obese group showed a higher AUC value than the underweight and lean group in ALN evaluation, although not significantly (2D-MLO: 0.7643 vs. 0.6458, P = .2656; 2D-axilla: 0.8083 vs. 0.6586, P = .1522; 3D-axilla: 0.8045 vs. 0.6615, P = .1874). This difference was more pronounced in axilla view. CONCLUSION: Axilla view exhibited advantages over conventional MLO view in the extent of axilla displayed by mammography in breast cancer. Further studies with larger sample sizes are needed.

B Cells and IL-21-Producing Follicular Helper T Cells Cooperate to Determine the Dynamic Alterations of Premetastatic Tumor Draining Lymph Nodes of Breast Cancer.

Metastasis is the major cause of cancer-related death, and lymph node is the most common site of metastasis in breast cancer. However, the alterations that happen in tumor-draining lymph nodes (TDLNs) to form a premetastatic microenvironment are largely unknown. Here, we first report the dynamic changes in size and immune status of TDLNs before metastasis in breast cancer. With the progression of tumor, the TDLN is first enlarged and immune-activated at early stage that contains specific antitumor immunity against metastasis. The TDLN is then contracted and immunosuppressed at late stage before finally getting metastasized. Mechanistically, B and follicular helper T (Tfh) cells parallelly expand and contract to determine the size of TDLN. The activation status and specific antitumor immunity of CD8+ T cells in the TDLN are determined by interleukin-21 (IL-21) produced by Tfh cells, thus showing parallel changes. The turn from activated enlargement to suppressed contraction is due to the spontaneous contraction of germinal centers mediated by follicular regulatory T cells. On the basis of the B-Tfh-IL-21-CD8+ T cell axis, we prove that targeting the axis could activate TDLNs to resist metastasis. Together, our findings identify the dynamic alterations and regulatory mechanisms of premetastatic TDLNs of breast cancer and provide new strategies to inhibit lymph node metastasis.

Percutaneous microwave ablation combined with endocrine therapy versus standard therapy for elderly patients with HR-positive and HER2-negative invasive breast cancer: a propensity score-matched analysis of a multi-center, prospective cohort study.

Background: There is a growing trend to apply minimally invasive local treatments for elderly patients with early-stage breast cancer. As a minimally invasive thermal therapy, microwave ablation (MWA) has been attempted to treat breast cancer of small lesions, but its long-term local efficacy on elderly patients has seldom been reported. In this study, we aimed to compare outcomes of MWA combined with endocrine therapy to standard surgery combined with adjuvant therapy in the treatment of hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer for elderly patients. Methods: This prospective multi-center cohort study enrolled patients over 70 years old diagnosed with HR-positive and HER2-negative early-stage invasive breast cancer between January 2016 and July 2021. Patients chose either non-randomized to undergo MWA combined with endocrine therapy (MWA group) or standard surgery combined with adjuvant therapy (surgery group). Endpoints for the comparisons were disease-free survival (DFS), overall survival (OS) and length of hospital stay (LOS) after adjusting for previously reported risk factors using propensity score matching (1:3). Results: Of the enrolled 132 patients, 33 were in the MWA group and 99 were in the surgery group. MWA was successfully performed in all cases, and technical effectiveness was achieved in all cases. With a median follow-up of 31 months, only one case had local recurrence 23 months after MWA. MWA combined with endocrine therapy and standard surgery combined adjuvant therapy for elderly patients with breast cancer achieved similar DFS [hazard ratio, 0.536; 95% confidence interval (CI): 0.128-2.249] and OS (hazard ratio, 0.537; 95% CI: 0.089-3.235). Besides, MWA had much shorter LOS than standard surgery (7.1 versus 13.0 days, P<0.001). Conclusions: MWA combined with endocrine therapy and standard surgery combined with adjuvant therapy for elderly breast cancer patients achieved similar outcomes. MWA combined with endocrine may be a feasible treatment strategy for elderly patients with HR-positive and HER2-negative invasive breast cancer.

Local and systemic therapy may be safely de-escalated in elderly breast cancer patients in China: A retrospective cohort study.

Background: For elderly patients with breast cancer, the treatment strategy is still controversial. In China, preoperative axillary lymph node needle biopsy is not widely used, resulting in many patients receiving axillary lymph node dissection (ALND) directly. Our study aims to determine whether local and systemic therapy can be safely de-escalated in elderly breast cancer. Methods: Patients aged ≥70 years were retrospectively enrolled from our institution's medical records between May 2013 and July 2021. Groups were assigned according to local and systemic treatment regimens, and stratified analysis was performed by molecular subtypes. Univariate and multivariate survival analyses were used to compare the effects of different regimens on relapse-free survival (RFS). Results: A total of 653 patients were enrolled for preliminary data analysis, and 563 patients were screened for survival analysis. The mean follow-up was 19 months (range, 1-82 months). Axillary lymph node metastases were pathologically confirmed in only 2.1% of cN0 cases and up to 97.1% of cN+ cases. In the aspect of breast surgery, RFS showed no significant difference between mastectomy and BCS group (p = 0.3078). As for axillary surgery, patients in the ALND group showed significantly better RFS than those in the sentinel lymph node biopsy (SLNB) group among pN0 patients (p = 0.0128). Among these cases, the proportion of cN+ in ALND was significantly higher than that in SLNB (6.4% vs. 0.4%, p = 0.002), which meant axillary lymph nodes (ALNs) of ALND patients were larger in imaging and more likely to be misdiagnosed as metastatic. With regard to adjuvant therapy, univariate and multivariate analyses showed that RFS in different comprehensive adjuvant regimens were similar especially among hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)- subgroup where patients who did not receive any adjuvant therapy accounted for 15.7% (p > 0.05). Conclusions: It is feasible to reduce some unnecessary local or systemic treatments for elderly breast cancer patients, especially in HR+/HER2- subtype. Multiple patient-related factors should be considered when making treatment plans.