Breast Cancer Research and Treatment最新文献

Background: Understanding locoregional recurrence (LRR) risk is important in breast cancer, as it relates directly to breast cancer-associated mortality. Individualised LRR risk estimation should inform treatment and surveillance strategies. Increased mammographic breast density has been identified as a risk factor for the development of breast cancer. However, the precise relationship between mammographic density and breast cancer LRR remains unclear.

Aims: To perform a systematic review and relative risk meta-analysis to explore the assocation between breast mammographic density and breast cancer LRR.

Methods: A systematic review was performed as per PRISMA guidelines. Mammographic breast density (MBD) was classified as BI-RADs A-B (breast density < 50%, predominately fatty or scattered areas of fibroglandular density) or BI-RADs C-D breast density > 50%, heterogeneously dense or extremely dense). A meta-anlysis was performed using Meta-Disc and Statsdirect 2.8.0.

Results: Seven studies published between 2004 and 2023 met the inclusion criteria, comprising 3008 patients with reported mammographic breast density (MBD) (age range: 20-94 years). Overall, 59.1% (1779/3008) were classified as low MBD (BI-RADS A-B) and 40.9% (1229/3008) were classified as high MBD (BI-RADS C-D). Of these patients, 68.9% (2073/3008) were treated for invasive breast carcinoma and 31.1% had ductal carcinoma in-situ (DCIS). Breast-conserving surgery (BCS) was performed in 71.1% (2139/3008) of patients, mastectomy was performed in 28.2% (850/3008),. The median follow-up was 94.1 months, and the overall LRR rate was 12.8% (386/3008). Five of the seven studies reported a correlation between BI-RADs C-D and the development of LRR. LRR rates were lower in patients with low mammographic breast density (9.9% for BI-RADS A-B (177/1779)) compared to those with higher mammogaphic breast density (17.0% for BI-RADs C-D. (209/1229)) [P < 0.001, Chi Square]. BI-RADS C-D density on mammography was associated with an increased risk of locoregional recurrence (pooled relative risk 1.41; 95% confidence interval 1.17 to 1.70).

Conclusion: Increased mammographic breast density may be associated with an increased risk of LRR. Multidisciplinary team discussions should consider MBD as a potential prognostic factor in when considering surveillance and locoregional control after breast cancer treatment.

Background: Previous studies often combined double hormone receptor-positive (dHR +) and single HR-positive (sHR +) tumors, thus not accounting for the distinct characteristics of sHR + , particularly in the neoadjuvant setting. Moreover, adding immunotherapy to cytotoxic chemotherapy has shown encouraging efficacy in certain HR-positive early breast cancers. This study sought to assess pathological complete response (pCR) and survival outcomes in sHR + /HER2- breast cancer after neoadjuvant chemotherapy, while also investigating its specific biological traits and immune profile.

Methods: Clinical data were sourced from the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS, n = 1049), and the Surveillance, Epidemiology, and End Results (SEER, n = 21,092) database to examine neoadjuvant chemosensitivity and survival outcomes. Additionally, clinicopathological and subtype data from CHCAMS, SEER, the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1052), and Fudan University Shanghai Cancer Center (FUSCC, n = 570) were analyzed to identify biological features that correlate with pCR rates and prognosis in sHR + /HER2- breast cancer. Further genomic and transcriptomic data from METABRIC, The Cancer Genome Atlas (TCGA, n = 741), and MSK-IMPCAT (n = 1535) were reviewed to uncover their potential links with endocrine and immunotherapy responses.

Results: In comparison to dHR + (ER + and PR +)/HER2- breast cancer, sHR + (ER + /PR- or ER-/PR +)/HER2- breast cancer displayed a higher pCR rate (20.2% vs. 3.2%, P < 0.001), but considerably worse survival (hazard ratio, 2.97; 95% confidence interval, 1.62-5.43, P < 0.001) within the CHCAMS neoadjuvant cohort. Clinically, sHR + /HER2- tumors were associated with higher histological grades and proliferation rates compared to dHR + /HER2- tumors, along with a greater rate of HR-low positivity (50.9% vs. 3.0%, P < 0.001) in primary tumors and a tendency to transition to triple-negative tumors in residual disease (42.7% vs. 1.8%, P < 0.001). Furthermore, sHR + /HER2- breast cancers demonstrated lower endocrine sensitivity scores, with about 20% classified as PAM50-defined basal-like subtype. Immunologically, sHR + /HER2- tumors had elevated tumor mutation burden (TMB), higher expression of immune checkpoint genes (e.g., PD-1, PD-L1, CTLA4), and greater infiltration by tumor-infiltrating lymphocytes (TILs), particularly CD8 + T cells, than dHR + /HER2- tumors.

Conclusion: Compared to dHR + /HER2- breast cancer, sHR + /HER2- cases showed a relative sensitivity to neoadjuvant chemotherapy but poorer prognosis. The immune-activated phenotype of sHR + /HER2- breast cancer indicates that it may benefit from immunotherapy approaches, but these findings warrant validation in prospective studies.

Purpose: Black women with hormone receptor-positive (HR +) breast cancer are twice as likely as White women to have weakly HR + tumors (1-10% positive cells). Patients with weakly HR + tumors are less frequently prescribed ET and have 60% higher mortality than strongly HR + tumors (> 10% positive cells). We evaluated factors associated with ET prescription and self-reported use among Black women with HR + breast cancer.

Methods: Among 922 Detroit ROCS participants, we evaluated associations between demographics, socioeconomic status, and health, tumor, oncologist, and hospital characteristics and ET prescription intent and self-reported ET use. Logistic mixed-effects regression was used to account for oncologist and hospital group effects.

Results: Oncologists intended to prescribe ET to 83.4% of participants (n = 769), of which 54.4% (n = 502) reported use. In multivariable models, participants with weakly HR + tumors were 90% less likely to be prescribed ET (OR = 0.10, p < 0.0001). Other significant characteristics of ET prescription included a BMI of 25-29.9 kg/m² (OR = 0.45, p = 0.0085), HR positivity > 90% vs. 11-90% (OR = 0.37, p = 0.00045), unknown HR percentage (OR = 0.12, p < 0.0001), OncotypeDx testing (OR = 2.65, p < 0.0001), and receiving radiation (OR = 2.20, p = 0.00016). Self-reported ET use was lower among those with lower health literacy (OR = 0.017, p < 0.001), weak HR positivity (OR = 0.46, p = 0.0053), unknown HR percentage (OR = 0.074, p = 0.034), and older age at diagnosis (OR = 0.88, p = 0.002). Increased ET use was associated with an income between $60,000-$79,900 vs. < $20,000 (OR = 1.54, p = 0.035), higher comorbidity count (OR = 1.09, p = 0.0054), distant stage (OR = 2.03, p = 0.029), and surgery (OR = 2.35, p = 0.001).

Conclusion: Identifying multilevel factors related to ET use may inform strategies to improve ET uptake and survival among Black women with HR + breast cancer.

Purpose: Knowledge of the uptake and breast and ovarian cancer-preventive and survival effects of bilateral risk-reducing mastectomy (BRRM) and salpingo-oophorectomy (RR-BSO) in female BRCA1/2 carriers is essential for optimized decision-making. This study aimed to examine time trends in the number of registered unaffected BRCA1/2 carriers, BRRM and RR-BSO uptake, and oncological effects of risk-reducing surgeries in a nationwide Danish cohort with matched controls.

Methods: We included 3067 female BRCA1/2 carriers registered in the Hereditary Breast and Ovarian Cancer Registry and 30,652 age-matched controls between 2000 and 2022. Data were retrieved from national health registries. Uptake and oncological effects of risk-reducing surgeries were assessed using cumulative incidences and Cox proportional hazards models with 95% confidence intervals (CI).

Results: Annual numbers of registered unaffected BRCA1/2 carriers, BRRM, and RR-BSO increased over time. BRRM and RR-BSO uptake 10 years after genetic test varied with the age at genetic test and parity. BRRM reduced the hazard rate of breast cancer by 94% [hazard ratio (HR) 0.06, CI 0.01-0.25]. The same pattern was not found for RR-BSO (HR = 1.31, CI 0.90-1.91). Compared to controls, BRCA1/2 carriers had an increased hazard rate for breast cancer before BRRM (HR 7.49, CI 5.81-9.42).

Conclusion: BRRM's large protective effect against breast cancer in BRCA1/2 carriers was confirmed, in contrast to that of RR-BSO. There were tendencies toward a reduction in overall mortality rates after BRRM, and compared with controls, we saw tendencies toward higher mortality rates before BRRM.

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: 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.