Purpose: This study aimed to examine the impact of the level of HER2 overexpression on pathologic and clinical outcomes in HER2-positive breast cancer (BC) patients treated with neoadjuvant therapy (NAT).
Methods: Women with Stage II or III HER2-positive BC who received anthracycline-taxane-trastuzumab NAT regimens followed by curative-intent surgery were included. Patients were classified according to tumor HER2 expression into HER2-high (immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) HER2/CEP17 ratio ≥5 or HER2 copy number ≥10) and HER2-intermediate (IHC 2+ with HER2/CEP17 ratio ≥2 to <5 or copy number ≥4 to <10). Univariate and multivariate logistic regression analyses were performed using HER2 expression as a categorical variable. The primary outcome was pathological complete response (pCR). Estimated 3-year disease-free survival (DFS) and Overall Survival (OS) were secondary outcomes.
Results: Among 161 patients with HER2-positive BC, 139 (86%) and 22 (14%) were classified as HER2-high and HER2-intermediate, respectively; 105 (65.2%) had hormone receptor (HR)-positive tumors; 72 (45%) achieved a pCR. In the overall population, pCR rates of 18% and 49% were achieved in HER2-intermediate and HER2-high cases, respectively (odds ratio [OR] = 0.23 95% CI 0.07-0.72; P = .007). No pCRs were observed among HR-positive, HER2-intermediate cases. Estimated 3-year DFS was 97.1% versus 89.3% for patients achieving a pCR versus those with residual disease, respectively (P = .0011).
Conclusion: We found that patients with HER2-high disease were more likely to achieve pCR after NAT compared to patients with HER2-intermediate BC, a subgroup of patients that may benefit from more personalized NAT strategies.
Background: Breast cancer continues to pose a significant public health challenge, with its incidence and disproportionate impact on underserved populations in the United States. The relationship between obesity and clinicopathological characteristics at presentation remains a critical area of investigation. Safety-net hospitals caring for underserved communities provide a unique setting to explore these associations. This study seeks to explore a critical gap in knowledge on obesity and breast cancer characteristics in underserved populations in the United States.
Materials and methods: In this retrospective study, 927 breast cancer patients were included. Analysis was conducted to assess the association between body mass index (BMI), age of diagnosis, tumor clinicopathologic characteristics, and molecular types stratified by menopausal status at diagnosis. Analysis was performed using the Statistical Package for Social Sciences version 29.
Results: A significant association was found between BMI and menopausal status (P < .05). Disease stage at presentation was significantly associated with BMI (P < .05). Further investigation into BMI categories and tumor characteristics revealed a significant correlation in postmenopausal women, with obesity linked to tumor size and lymph node status (P < .05). No significant associations were observed between HER-2 status, ER/PR status, and obesity in either premenopausal or postmenopausal groups.
Conclusion: This observational retrospective hypothesis-generating study revealed the association between obesity and disease stage and menopause status at diagnosis. In postmenopausal patients, obesity correlated with larger tumor size and advanced lymph node disease involvement. Additionally, ethnic variations were observed, with a higher prevalence of obesity among African American patients.
Background: Alpelisib is an oral α-specific class I PI3K inhibitor approved in combination with fulvestrant for the treatment of PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. The tolerability of this drug with the oral chemotherapy capecitabine is unknown.
Patients and methods: This phase I trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of alpelisib (250 mg or 300 mg daily for 3-weeks) with capecitabine (1000 mg/m2 twice daily for 2-weeks followed by a 1-week rest period) in patients with metastatic HER2-negative breast cancer, regardless of PIK3CA mutation status.
Results: Eighteen patients were treated with alpelisib-capecitabine. Half of the patients had HR+ breast cancer, and 16 had prior systemic therapy for metastatic disease. The MTD of alpelisib was 250 mg daily in combination with capecitabine 1000 mg/m2 twice daily. DLTs included hyperglycemia, QTc prolongation, fatigue, and chest pain. The most common grade 3 adverse event (AE) was hyperglycemia (28%). No grade 4 AEs were observed. Three patients discontinued therapy due to an AE. One-third of patients required dose reduction of both alpelisib and capecitabine. Four patients experienced a partial response and 8 patients experienced stable disease. The median progression-free survival was 9.7 months (95% CI 2.8-13.5 months) and median overall survival was 18.2 months (95% CI 7.2-35.2 months). Twelve patients had PIK3CA mutation testing completed, of these 2 had known or likely deleterious PIK3CA mutation.
Conclusion: This study provides safety data for an oral combination therapy of alpelisib-capecitabine and defines tolerable doses for further study.
Background: Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer, with 5-10% of cases progressing into invasive disease. Herein, we investigated the association between HER2-low and clinico-pathological characteristics in DCIS and subsequent ipsilateral loco-regional relapse (LRR).
Materials and methods: We accessed our prospectively maintained institutional database. HER2 status was determined by immunohistochemistry and classified as null (score 0), over-expressed (3+), and low (1+ or 2+); in situ hybridization was not considered since it is not used for routine DCIS diagnostics.
Results: Among 375 patients with DCIS, median age was 54 (27-88) years, with a primary tumor size < 2.5 cm in 63%, grade III in 33%, and positive hormone receptor status (HR) in 81% of cases; 71% underwent breast-conserving surgery, 34% received adjuvant endocrine and 39% radiotherapy. A total of 197 (52%) had tumors with low HER2 expression, which resulted significantly associated with grade I/II (P < .001), Ki67< 20% (P < .001), and HR-positive status (P < .001). HER2-low distribution varied from 19.61% and 50% in ER negative and ER-low (<10%) to 60% and 69% in ER high (50%-95%) and very high tumors (> 95%) (P < .001). After a median 39-month follow-up (IQR 16-65), cumulative incidences of LRR was 0.054. Among 17 patients with paired primary tumor and LRR, 5 had discordant HER2 status, with an even distribution of increased and decreased HER2 expression.
Conclusions: Low HER2 expression in DCIS is associated with features of reduced aggressiveness. Importantly, changes in HER2 expression may occur prompting retesting in recurrent cases, in line with observations in invasive breast cancer.
Objective: This study aimed to investigate the effect of a combination of functional exercise and psychological interventions on postoperative rehabilitation and intervention compliance in patients with breast cancer (BC).
Methods: This study involved 100 patients with BC who underwent a radical mastectomy in our hospital between April 2020 and April 2021. We assigned patients to a control group (with a functional exercise intervention for patients) and an observation group (where patients received psychological interventions based on functional exercise) using a random number table. We observed and recorded the general data, intervention compliance, range of motion (ROM) of the shoulder joint pre and postintervention, pre and postintervention quality of life scores, and anxiety and depression scores before and after the interventions.
Results: There were no significant differences in general data between the 2 groups (P > .05). Repeated measures analysis showed no preintervention differences in compliance, shoulder ROM, quality of life, or anxiety and depression scores (P > .05). Postintervention, compliance and shoulder ROM improved in both groups, with the observation group significantly outperforming the control group (P < .05). Quality of life scores improved significantly in both groups, with higher scores in the observation group at 1 and 3 months (P < .05). Anxiety and depression scores decreased in both groups, with the observation group showing lower scores than the control group (P < .05).
Conclusion: Combining functional exercise with psychological interventions improves treatment compliance, psychological status, postoperative shoulder ROM, and quality of life in breast cancer patients.
In 2016 the Choosing Wisely guidelines advised against routine performance of a sentinel lymph node biopsy (SLNB) in women ≥ 70 years of age with clinically node negative (cN0), early-stage, oestrogen receptor positive/ human epidermal growth factor receptor 2 negative (ER+/HER2-), invasive breast cancer. The argument in favour of its continued performance is that it may serve as a useful guide for subsequent management. This systematic review was performed in accordance with the PRISMA guidelines. Studies reporting on rate of adjuvant chemotherapy, adjuvant radiotherapy and performance of completion axillary lymph node dissection (cALND) post SLNB in women aged ≥ 65 years with cN0, early-stage, ER+/HER2-, invasive breast cancer were included. A random effects meta-analysis was performed with summary estimates made using the Mantel-Haenszel method. Dichotomous outcomes were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Ten retrospective studies across 4 countries. Of 105,514 patients, 15,509 had a positive SLNB and 90,005 had a negative SLNB. On meta-analysis, a positive SLNB was significantly associated with receipt of adjuvant chemotherapy (OR 4.64 (95% CI 3.18, 6.77), P < .00001), adjuvant radiotherapy (1.71 (95% CI 1.18, 2.47), P = .005) and undergoing completion axillary lymph node dissection (OR 68.97 (95% CI, 7.47, 636.88), P = .0002). Adjuvant treatment decisions continue to be influenced by SLNB positivity in the era of the Choosing Wisely guidelines. The effects of a positive SLNB and subsequent treatments on outcomes remain inconclusive. However, it is likely clinicians are continuing to over-investigate and over-treat this cohort.