Breast Cancer Research and Treatment最新文献

Purpose: To evaluate the effect of body mass index (BMI) on oncologic outcomes in patients with breast cancer stratified by menopausal status and histological subtype. Although studies have focused on the relationship between obesity and breast cancer risk, the association between BMI and breast cancer recurrence after surgery remains controversial.

Methods: This retrospective study included patients who underwent curative surgery for breast cancer between June 2003 and November 2017. Normal weight and overweight groups were defined based on the World Health Organization classification. The primary outcome was recurrence-free survival, evaluated at 1, 5, and 10 years after curative surgery. Patients were stratified by BMI category, histological subtype, and menopausal status. The main measures included tumor characteristics, recurrence events, and survival outcomes across groups.

Results: Among 4506 patients included in the analysis, 3384 (75.1%) had luminal-type breast cancer. The overweight group (n = 1259) was associated with older age (normal weight (NW): 50.2 ±10.9 vs. overweight (OW): 56.5 ± 1.9, P < 0.001) and higher T stage (≥ T2: NW: 1226 (37.7%) vs. OW: 577 (45.8%), P < 0.001). In patients with luminal-type breast cancer, 10-year recurrence-free survival was significantly worse in the overweight group (NW 89.3% vs. OW 85.7%, P = 0.018). Subgroup analysis showed that premenopausal patients with luminal-type breast cancer who were overweight had an increased risk of recurrence (P = 0.003).

Conclusions: Obesity is a significant, potentially modifiable risk factor for recurrence in premenopausal females with luminal-type breast cancer.

Purpose: Postoperative infection rates in the United States following breast cancer surgery, including mastectomy with or without reconstruction, range from 2-26%. Management of post-lumpectomy defects may involve simple skin closure or oncoplastic closure; however, the effect of defect repair on postoperative infection rates has not been well documented. Here we determine how oncoplastic closure of partial mastectomy defects affects postoperative infection rates and antibiotic use.

Methods: In this retrospective single-institution study, patients undergoing lumpectomy with and without oncoplastic closure of defect were included between 2018-2020. Clinicopathologic/treatment data were collected from medical records. Patients receiving antibiotics on postoperative days 5-30 were reviewed to confirm wound infection. Associations between demographic and clinicopathologic factors and postoperative infections were analyzed.

Results: 3937 patients met eligibility criteria; 2273 (58%) had oncoplastic closure. The overall postoperative wound infection rate (includes cellulitis) was 8.4% (332), and true surgical site infection, as defined by the CDC (excludes cellulitis), was seen in 70 (1.8%) patients. On univariate analysis, age ≥ 60 years, diabetes, hypertension, and BMI ≥ 30 were associated with increased breast infection. Oncoplastic closure was protective against postoperative breast infections (odds ratio [OR]0.70, p = 0.040). On multivariable analysis oncoplastic closure had marginally decreased breast infection rates (OR 0.71, p = 0.053); however, this was not significant. BMI ≥ 30 was the only risk factor that remained a significant predictor of increased breast infection rates (OR1.63, p = 0.021).

Conclusions: Oncoplastic closure of lumpectomy defects had marginally significant lower rates of postoperative breast infections. As oncoplastic techniques are increasingly adopted in breast-conserving surgery, it is important to further study the protective nature of lumpectomy defect closure to reduce postoperative infection rates.

Purpose: The Promoting Resilience in Stress Management (PRISM) intervention is a brief, positive psychological skills-based intervention delivered by lay-coaches with demonstrated efficacy at decreasing distress in young adults with cancer. We recently completed a pilot trial of "PRISM for women with breast cancer" (PRISM-BC) and demonstrated feasibility. Here, we conducted qualitative analyses to better understand the experiences of women who participated in PRISM-BC.

Methods: For this single-armed, pilot study of PRISM-BC, we recruited women who were receiving chemotherapy for any stage of breast cancer. All received the PRISM intervention, including six individual, virtual sessions and access to a companion mobile app for skill practice. Following PRISM completion, participants completed a 30-60-minute semi-structured, qualitative interview. We employed coding reliability thematic analysis to identify themes, with two team members applying codes to ensure satisfactory inter-rater reliability.

Results: Women (N=33) were on average 54.1 years old (SD=9.5); most had early stage disease (76%), identified as Black/African American (58%), and downloaded the companion app (70%). We identified four themes: 1) PRISM was helpful due to both new skill acquisition and experiential relevance; 2) The app was helpful to many, but barriers prevented use among some; 3) Both facilitators and barriers to PRISM engagement were present; 4) Opportunities exist to tailor PRISM further to the specific needs of breast cancer survivors CONCLUSION: PRISM was well-received among women with breast cancer. Future work should examine the efficacy of PRISM in larger, controlled trials in breast oncology incorporating suggested modifications (e.g., content around medication adherence).

Purpose: We investigated outcomes of invasive lobular carcinoma (ILC) with or without concurrent lobular carcinoma in situ (LCIS) in patients with classic or pleomorphic ILC.

Methods: We retrospectively analyzed a single-institution database of patients with stage I-III ILC. We compared tumor features, treatment, and recurrence free survival (RFS) in patients with ILC-alone versus ILC + LCIS stratified by ILC tumor subtype. Multivariable Cox proportional hazards models were used for multivariate analysis.

Results: Of the 786 cases of ILC, 542 were classic and 92 were pleomorphic, with 70.6% overall having concurrent LCIS. Overall, ILC + LCIS cases were less often T3 (p = 0.037) and had lower rates of N2/N3 disease (p = 0.026) than ILC-alone. Concomitant LCIS was also associated with greater progesterone receptor (PR) positivity (p = 0.016), and was more commonly grade 2 and less often grade 1 compared to ILC-alone (p = 0.008). Treatment differed, with ILC + LCIS cases receiving less chemotherapy (p = 0.016) and more mastectomy (p = 0.015). Among patients with classic ILC, the presence of concomitant LCIS was not associated with different RFS. However, among those with pleomorphic ILC, ILC + LCIS was associated with significantly improved RFS compared to ILC-alone (HR 0.31, 95% confidence interval 0.10-0.96, p = 0.043).

Conclusion: While the presence of LCIS was not associated with RFS in classic ILC in this dataset, it is a favorable prognostic factor in pleomorphic ILC, suggesting a potentially differential role in ILC subtypes.

Background: Poly [ADP-ribose] polymerase (PARP) 1 enzyme is vital in DNA repair mechanisms. PARP1 inhibitors are in clinical use due to synthetic lethality in homologous-recombination repair-deficient tumors with germline BRCA1/2 mutations. Given that highly proliferative cancer requires excessive DNA replication and thus repair, we hypothesized that high PARP1 expression is associated with aggressive tumor biology in primary breast cancer regardless of subtype.

Methods: The gene expression profile of the primary breast cancer from 6351 patients from 3 independent cohorts (TCGA, METABRIC and SCAN-B) were analyzed by PARP1 expression. Transcriptomics data were analyzed in different subtypes of breast cancer separately. PARP1 high vs low expression groups was divided by the median in each cohort. PARP1 expression was also compared by response to neoadjuvant chemotherapy in 3 cohorts (GSE173839, GSE20566 and GSE20194).

Results: PARP1 expression varied significantly across breast cancer subtypes, with lower expression in hormone-receptor positive (HR +) patients. High PARP1 expression was linked to increased mutation burden, particularly in HR + tumors. It also correlated with increased activity across multiple DNA repair pathways and increased cell proliferation, with enrichment in pathways related to cell cycle. Additionally, high-PARP1 tumors exhibited greater immune cell infiltration, particularly in HR + cases. In neoadjuvant chemotherapy studies, higher PARP1 expression levels were seen in patients with pathologic complete response (pCR) rates after preoperative chemotherapy, especially in HR + subtype.

Conclusion: Expression of PARP1 gene is associated with aggressive cancer biology, especially in the HR + subtype of breast cancer, and may serve as a biomarker for response to chemotherapy.

Purpose: Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate (ADC) approved for the treatment of HER2-positive metastatic breast cancer (MBC). Despite its efficacy, eventual resistance and disease progression are common, and no prospective studies exist to guide therapy in T-DXd-resistant HER2-positive MBC.

Methods: This retrospective study analyzed patients with HER2-positive MBC who received cancer-directed therapies following treatment with T-DXd at Memorial Sloan Kettering Cancer Center.

Results: Eighty-one eligible patients were identified, who received 199 lines of therapy collectively. Post-T-DXd therapies included other ADCs, chemotherapy, HER2-targeted antibodies, hormone-based therapy, tyrosine kinase inhibitors (TKIs), and clinical trials. The median overall survival (OS) after stopping T-DXd treatment was 19 months, with a median progression-free survival (mPFS) of 3.7 months per subsequent treatment line. Chemotherapy was the most common treatment (42% of treatment lines; mPFS 3.4 months). No single therapeutic approach was clearly superior, although subsets of patients appeared to benefit from hormone therapy or TKIs. In a multivariate analysis including treatment type, treatment line, hormone receptor (HR) status, presence of brain metastases, and reason for T-DXd cessation, patients who discontinued T-DXd due to toxicity, rather than disease progression, had significantly better outcomes on subsequent therapy lines (HR 0.35; p < 0.001).

Conclusion: Our study indicates that patients emerge from T-DXd treatment with highly refractory disease. These findings highlight the urgent need for optimized treatment strategies and novel therapeutic options for this patient population.

Purpose: The COVID-19 pandemic was associated with a decrease in the incidence of breast cancers in 2020 and was expected to be associated with advanced stage at presentation in the post-pandemic era. The primary objective of this study is to compare stage at presentation and biological tumor characteristics of breast cancers treated before and after the initial phase of the COVID pandemic.

Methods: A retrospective chart review was performed of patients diagnosed with breast cancer within a single New York City health care system between March-August 2019 (pre-pandemic; PP) and March - August 2021 (post- acute phase pandemic; PAP).

Results: There were 381 patients with breast cancer in the 2019 PP cohort and 558 patients diagnosed in the 2021 PAP cohort. The PAP cohort was more likely to have a larger median tumor size (16 mm vs 12 mm, p < 0.001) and more tumors > 2 cm at surgery (OR 1.48, p = .048). PAP patients were more likely to have node positive disease at surgery (OR 2.54, p = 0.0003), grade 3 tumors (OR 1.29, p = 0.046) and pathologic stage II or III disease at upfront surgery (OR 2.89, p = 0.003). The PAP cohort was also more likely to have > 24 months since their last imaging test (p < 0.001) and less likely to have their breast cancer detected by screening breast MRI (OR .36, p = .016).

Conclusion: Breast cancer diagnosed in the post-acute pandemic period had a greater odds of having a > 24-month interval since their last screening mammogram and pathologic stage II & III disease than pre-pandemic patients.

Purpose: Prior studies have shown favorable post-surgical outcomes for patients with breast cancer treated at higher-volume hospitals. However, the impact of hospital volume on the management and outcomes for patients with locally advanced breast cancer (LABC) is unknown.

Methods: This retrospective study included 42,980 patients from the National Cancer Database (NCDB) with LABC treated between 2010 and 2017 at 1306 cancer-accredited centers. Centers were categorized as high-, medium-, and low-volume centers based on the number of patients with LABC seen annually. We assessed the association between hospital volume, receipt of trimodality therapy (TMT), and overall survival (OS), adjusting for demographic, clinical, and treatment variables.

Results: High-volume centers treated a median of 18.6 patients (range 15.4, 90.7) per year compared to 8.0 and 2.9 patients at medium- and low-volume centers, respectively. High-volume centers included more academic/research centers; served younger, higher-income, and racially diverse patients; and achieved higher rates of timely (within 60 days of diagnosis) neoadjuvant systemic therapy (NST) initiation and pathologic complete response (pCR) compared to low-volume centers (all P < .001). Treatment at high-volume centers (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.82, 0.97; P < .001) and receipt of recommended TMT (HR, 0.52; 95% CI 0.50, 0.54; P < .001) were independently associated with improved 5-year OS.

Conclusion: Higher hospital volume was associated with improved survival outcomes in patients with LABC, influenced by greater adherence to guideline-concordant care. Efforts should focus on enhancing the capacity of low-volume centers to replicate high-volume care standards, addressing access and outcomes for vulnerable populations.

Introduction: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with limited therapeutic options. Mesothelin (MSLN), a tumor-associated antigen with potential targeted drugs, has been reported to be positive in some TNBC patients. However, there is a lack of studies on the clinicopathological characteristics of MSLN-expressing TNBC.

Materials and methods: We first demonstrated the significance of MSLN through pan-cancer analysis. We utilized local cohort to demonstrated that MSLN is associated with an immunosuppressive microenvironment and patients with high MSLN expression have poorer response to neoadjuvant chemotherapy combined with immunotherapy. Moreover, MSLN-expressing TNBC exhibit extensive lymphovascular tumor thrombi. Furthermore, spatial transcriptomics investigated T1N3-stage TNBC and identified MSLN as a highly expressed target in this aggressive subtype, public single-cell data identified MSLN-expressing tumor sub-cluster and their characteristics.

Conclusion: This study provides novel insights into the role of MSLN in TNBC and lays the foundation for future therapeutic strategies targeting MSLN in this aggressive breast cancer subtype.

Introduction: Limited data is available on patients diagnosed with breast cancer at age 85 and older, and there is no consensus on mammographic screening guidelines for older women, including those with a history of breast cancer. We sought to describe characteristics of presentation in this patient population and to determine whether differences exist between older women with a history of breast cancer and those without.

Methods: A retrospective review was conducted of all female patients aged 85 and older who consulted a breast surgeon for a diagnosis of new or recurrent breast cancer.

Results: From January 1, 2009 to September 30, 2024, 132 patients with newly diagnosed or recurrent breast cancer were identified. Mean age was 88.3 years (range 85-99). Ninety patients (68.2%) were diagnosed with breast cancer for the first time and the remainder (42; 31.8%) had a history of breast cancer. 57.1% of patients with a history of breast cancer were diagnosed on screening imaging compared to 31.1% with no prior history, who more commonly were diagnosed based on symptoms. In patients with a history of breast cancer, there was a mean time of 14.6 years from index cancer to ipsilateral breast tumor recurrence and 19.2 years from index cancer to contralateral cancer event.

Discussion: Roughly one-third of patients had a prior breast cancer and were significantly more likely to be diagnosed on screening studies compared to women who did not have a history of breast cancer. Women without a history of breast cancer were more likely to be symptomatic at the time of diagnosis and more likely to be diagnosed at a later disease stage. In patients with a prior breast cancer, second breast cancer events tended to happen late, which raises the question of how long screening should continue after a breast cancer diagnosis in older patients and whether guidelines should distinguish between those with a prior history of breast cancer and those without.