An additional peril of pathologic complete response.

Introduction: Equitable access to healthcare is a fundamental principle of public health, aiming to ensure that all individuals have the opportunity to receive effective treatments. However, disparities in access to healthcare still persist in many countries, including Brazil. These disparities can have significant impacts on the health and well-being of patients, particularly in the case of breast cancer treatment. Neoadjuvant chemotherapy (NAC) has been increasingly used for the treatment of breast cancer, encompassing conditions ranging from locally advanced tumors to early-stage triple-negative and HER-2 positive tumors. Objectives: The aim of this study is to evaluate the impact of disparities in the use of trastuzumab (Herceptin) within the Brazilian public health system on pathological complete response (pCR), overall survival (OS), and disease-free survival (DFS). We aim to investigate whether variations in access to trastuzumab treatment influence the achievement of pCR and impact long-term survival outcomes in breast cancer patients. Methods: This retrospective, multicenter cohort study included female patients over 18 years of age with a diagnosis of non-metastatic breast cancer undergoing NAC. pCR was defined as the absence of residual invasive or in situ tumor in the breast and axilla. As an exploratory real-world data study, no confirmatory hypothesis was established, thus no corrections for multiple comparisons were necessary. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, calculated at five years. The study was approved by the Research Ethics Committee with registration number CAAE 64633422.4.0000.5463. Results: Between 2011 and 2020, a total of 1,891 patients were included in the study, of whom 454 (22.9%) were HER-2 positive. The pCR rate was 25.7%. Trastuzumab was accessed by 291 (64.1%) patients (p < 0.001). Among those who received trastuzumab, pCR was observed in 105 (36.1%) patients, compared to 12 (7.6%) in those who did not have access to trastuzumab (p < 0.001). OS in HER-2 positive patients was 90.1% with pCR and 64.5% without pCR (log-rank p < 0.001), while DFS was 89.2% with pCR and 68.2% without pCR (log-rank p = 0.003). Evaluating OS and DFS in patients who received trastuzumab versus those who did not, OS with trastuzumab and pCR was 94.3% and without pCR was 89.5% (log-rank p < 0.001); OS without trastuzumab and pCR was 83.3% and without pCR was 58.2% (log-rank p < 0.001). DFS in patients who received trastuzumab and achieved pCR was 94.5% and without pCR was 90.5% (log-rank p = 0.05), whereas without trastuzumab and pCR was 79.9% and without pCR was 62.1% (log-rank p = 0.001). Conclusion: These findings underscore the significant impact of disparities in trastuzumab utilization within the Brazilian public health system on pCR rates and long-term survival outcomes in HER-2 positive breast cancer patients. Access to trastuzumab was associated with higher pCR rates and improved overall and disease-free survival rates. Ensuring equitable access to targeted therapies is crucial for improving treatment response and long-term outcomes in breast cancer patients. Table 1 Clinicopathological characteristics of patients Legend: AJCC, American Joint Committee on Cancer; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; HR hormonal receptor. Table 2 - NAC schemas and correlation with pCR. AC-T, doxorubicin + cyclophosphamide – taxane; AC-TH, doxorubicin + cyclophosphamide – taxane+herceptin. Citation Format: Marcelo Antonini, Andre Mattar, Gabriel Pannain, Fernanda Grace Bauk Richter, Andressa Amorim, Marina Diogenes, Odair Ferraro, Luiz Gebrim, Reginaldo Coelho Lopes, Juliana Real. From Real-World Data to Improved Outcomes: Examining the Impact of Trastuzumab Disparities on Pathological Complete Response and Long-Term Survival in HER-2 Positive Breast Cancer Patients within the Brazilian Public Health System [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-06.

Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials

1017 Background: Pathologic complete response (pCR) of tumors in the breast and axillary lymph nodes (ALN) after primary systemic chemotherapy (PST) is associated with an excellent outcome. A previous analysis showed superior 5-year overall survival (OS) and relapse-free survival (RFS) for patients who achieved an ALN pCR after PST compared to those without a pCR in 5 prospective clinical trials. This study is an expanded analysis of all patients treated with PST at our institution examining the impact of ALN pCR on 10-year OS and RFS. Methods: Patients with clinical stage II/III and pathologically confirmed ALN metastases who underwent PST were categorized into 1 of 2 groups: ALN pCR and ALN residual disease. Additional data were collected, including breast cancer subtype, clinical tumor size, and lymph node staging, pathologic tumor (T) stage, and class of PST. RFS and OS were estimated by the Kaplan-Meier product limit method. Subset analyses were performed on patients with HER2-positive cancer. Results: 1,600 women diagnosed between 1989 and 2007 were identified. Median follow-up was 79 months (5-277); 454 (28.4%) achieved an ALN pCR. ALN pCR was associated with triple-negative and higher grade cancers, lower clinical stage, and lower pathologic breast T stage. 5-year OS and RFS estimates were similar to prior analysis. The 10-year OS was 85% and 58% and the 10-year RFS 83% and 55% (p < 0.001), for patients who achieved an ALN pCR and those with residual ALN disease. For HER2-positive breast cancers, 67.3% of patients who received HER2-targeted therapy achieved an ALN pCR vs. 32.3% without HER2-targeted therapy (p < 0.001). For patients receiving HER2-targeted therapy for HER2-positive breast cancer (n = 153), the 10-year OS was 92% and 52% (p = 0.006), and the 10-year RFS was 89% and 59% (p < 0.001) for those with and without an ALN pCR. Conclusions: ALN pCR is an excellent early surrogate marker for long-term outcome, 10-year RFS and OS. In HER2-positive breast cancers, HER2-targeted therapy is associated with high rates of pCR. Despite the aggressive nature of their disease, patients who achieve ALN pCR with PST have an excellent 10-year prognosis.

Background: Lymphovascular invasion (LVI) is known to be associated with a poor outcome in breast cancer patients. It indicates a highly proliferative cancer. Few studies examined the value of LVI as a predictor for outcome after neoadjuvant chemotherapy (NAC). The aim of this study to look for an association between survival outcomes and clinicopathological features in locally advanced breast cancer patients treated with NAC and to identify the predictors of nodal pathologic complete response (PCR). Methods:This study is a retrospective analysis of 224 women with locally advanced breast cancer who underwent NAC between 2011-2020. Kaplan-Meier analyses were used to assess the associations between disease-free survival (DFS) and overall survival (OS) and all clinicopathological variables including LVI in breast surgical specimens following NAC. Associations between nodal PCR and all clinicopathologic variables were assessed Results:Median follow-up was 29.9 months. Absence of nodal PCR (p.000), positive family history (p .027), clinical T4 (p.049), pathological TNM staging (p.016), high tumor grade (p .020),triple negative disease(p .016) and absence of tumor PCR (p.001) were associated with worse disease free survival. Absence of nodal PCR (p.002), high BMI (p.039), multicentric disease (p.026), high tumor grade, triple negative disease (p.018), and absence of tumor PCR (p.005) were associated with worse overall survival. LVI was found in 53 of surgical specimens (23.7%). It was associated with worse DFS (HR) (2.967) 95% CI (1.7-4.9), p.000 and overall survival (HR) (3.05) 95% CI (1.525-6.09), p.002). Nodal PCR significantly correlated with T stage (p .013), LVI (p.000), ER status (p.004), PR status (p.003), Her2neu status and IHC score (p.000), tumor subtype (p.000), tumor PCR (p.000), DFS (p.000), and OS (p.000). Conclusion:LVI is significantly associated with worse DFS and OS in locally advanced breast cancer patients treated with NAC. This data confirmed the previously published recommendation to add LVI to the pathological staging system. LVI may be further explored as a guide for adjuvant treatment options in clinical trials. Nodal PCR is another significant predictor of outcome and is associated significantly with tumor PCR and LVI. Both tumor PCR and LVI can be used as criteria for axillary surgery omission in future trials. Citation Format: Omima Elemam, Khaled Elnaghi, Ziad Emarah, Hossam Alghanami, Seham Abdelkhalek. Residual lymphovascular invasion: Predicts the outcome of neoadjuvant chemotherapy in locally advanced breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-30.

Neoadjuvant trials provide endpoints, such as pathological complete response (pCR) to treatment, that will potentially translate into meaningful improvements in overall survival and disease-free survival. Neoadjuvant trials need smaller sample sizes and are less expensive, and the endpoint of pCR is achieved in months, rather than years. For these reasons, the neoadjuvant setting is ideal for testing emerging targeted therapies in early breast cancer. Recently the US Food and Drug Administration has released a draft Guidance to Industry, outlining a pathway to accelerated approval for neoadjuvant breast cancer therapies using pCR. The association between pCR and outcome is clear for chemotherapy in triple-negative breast cancer and for HER2-targeted agents in HER2-positive disease, but might not hold true for other tumor subtypes such as luminal cancers. Since pCR is rarely achieved with either chemotherapy or endocrine therapy in hormone-receptor-positive breast cancer, in this setting we need to identify different intermediate endpoints, which might be translational endpoints within "window-of-opportunity," "residual disease," and "genome forward" trials. Prospective validation of effective noninvasive techniques for monitoring of residual disease burden could enhance the ability to identify promising targeted therapies in the neoadjuvant setting.

PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR). Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5%) and overexpression (≥5%). Patients’ responses were graded according to the Miller–Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR (P = 0.2). However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens (P = 0.02). Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B over-expression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded.

Safety of adjuvant CDK4/6 inhibitors during the COVID-19 pandemic.

e12540 Background: An inflammatory state in various cancer populations may correlate with mortality. Neutrophil-lymphocyte ratio is a surrogate marker of an inflammatory state. A recent meta-analysis showed the predictive value of neutrophil to lymphocyte ratio in breast cancers, but series are generally small. We aim to study the associations of Neutrophil-Lymphocyte Ratio (NLR) with outcomes in stage I–III breast cancer in patients who received neo-adjuvant chemotherapy (NAC) or upfront surgery. The endpoints are overall survival (OS) and breast cancer-specific survival (BCSS). In the NAC group, association with pathological complete response (PCR) rate was also studied. Methods: Data of patients with stage I–III breast cancer treated from 2011–2017 were extracted from a prospectively maintained registry and merged with full blood count (FBC) results from a clinical management software. FBC were performed within one-month pre-chemo for NAC patients and one-month pre-surgery for upfront surgery patients. PCR is defined as stage ypT0/isN0M0. OS is defined as death from any cancer from diagnosis date, censored at last follow-up. BCSS is defined as death from breast cancer from diagnosis date, censored at last follow up or death from any cause. The NLR values with the maximal Youden’s indexes calculated for each outcome were used as cut-off, logistic regression was used to determine PCR association and cox regression and log rank for OS and BCSS. Results: A total of 2,479 eligible patients were analysed. Overall, treatment compliance was high (87.6% of ER+ patients received endocrine treatment, and 94.1% of HER2+ NAC patients had targeted therapy). In the NAC group (n = 357), 23% achieved PCR. NLR did not show any statistically significant association with PCR. In unadjusted analysis, high NLR was associated with worse BCSS (log-rank p = 0.003 figure 1). In multivariable analysis (MVA), only triple negative and HER-enriched cancers were significantly associated with PCR. In NAC patients, NLR was associated with OS (cut-off 2.63; OR 1.6, p = 0.077) and BCSS (cut-off 3.58; OR 2.2, p = 0.003) in MVA. In patients treated with up-front surgery (n = 2122), unadjusted analysis showed high NLR was associated with worse BCSS (OR 1.55, p = 0.05; figure 2). In MVA, NLR (cut-off 2.13, OR 1.57, p = 0.005), triple negative histology, stage and age were significant predictors of OS. BCSS was not significantly associated with NLR (OR 1.38 95%CI 0.90-2.12 p = 0.145). Conclusions: Using a large cohort of patients, a high NLR was found to be associated with worse outcomes in NAC and upfront surgery breast cancer patients.

Purpose This study aimed to evaluate and compare tumor response rates and survival outcomes between single and double hormone receptor (HR) positive (+) [Estrogen Receptor (ER+)/Progesterone Receptor (PR) negative (-) or ER-/PR+ versus ER+/PR+] breast cancer (BC) patients with any HER2 status treated with neoadjuvant chemotherapy at a single institution Methods A retrospective review was conducted using the Sunnybrook “Biomatrix” database to identify eligible patients. A multivariable logistic regression analysis (MLR) was performed to assess the association between HR status (single or double HR+) and pathologic complete response (pCR) rates at surgery. A Kaplan-Meier method was used to estimate Disease Free Survival (DFS) and a log-rank test was used to compare DFS between 3 subgroups of patients: single or double HR+ and HR negative patients Results Three hundred and four BC patients were identified and included in the analysis with a median follow up of 43.3months (Q1-Q3: 28.7-61.1) and a mean age of 49.7 years (Standard deviation 10.9). Forty seven percent (47/101), 31% (11/36) and 14% (24/167) of patients with HR negative, single HR+ and double HR+ disease achieved a pCR respectively (X2 test &amp;lt;0.0001). In a MLR analysis, HR status and HER2 status were associated with pCR rates. Compared to HR negative patients, patients with double HR+ disease were less likely to achieve pCR (Odd ratio (OR):0.14, 95%CI 0.06-0.31, p&amp;lt;0.0001) while single HR+ patients did not differ (OR:0.51, 95%CI 0.19-1.4). The association between HR+ status (single versus double HR+) and pCR rates compared to HR negative patients remained the same in subgroup analyses of HER2+ and HER2 negative patients separately. No difference in survival (DFS) was seen between the 3 subgroups of patients: HR negative, single and double HR+ patients. Conclusion BC patients with single HR+ disease behave differently than double HR+ patients in terms of likelihood of achieving pCR after neoadjuvant chemotherapy and do not differ from HR negative patients. This difference does not translate into a difference in DFS. Prospective studies are needed to validate these findings before considering different treatment strategies for these 2 subgroups of HR+ BC patients. Citation Format: Raphael J, Nofech-Mozes S, Trudeau ME. Clinical outcomes of single versus double hormone receptor positive breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-34.

Triple-negative breast cancer (TNBC) tumors do not express estrogen, progesterone or HER2/neu-receptors. There are no specific treatment guidelines for TNBC patients, however, it has been postulated that their phenotypic and molecular similarity to BRCA1-associated cancers would confer sensitivity to certain cytotoxic agents, including platinum. The aim of this meta-analysis was to evaluate the clinical outcome of breast cancer patients treated with platinum-based chemotherapy who had TNBC compared with those with non-TNBC. Electronic (MEDLINE, EMBASE and Cochrane Library databases) and manual searches were conducted throughout December 2011 to identify trials evaluating the use of platinum-based chemotherapy for patients with breast cancer. The methodological quality was assessed in accordance with the QUOROM statement. Seven studies met the eligibility criteria, with a total of 717 patients. Of these patients, 225 were TNBC patients (31%), 492 were non-TNBC patients (69%), 275 received platinum-based neo-adjuvant chemotherapy and 442 had advanced/metastatic breast cancers. The results showed that during neo-adjuvant chemotherapy, the clinical complete response (cCR) rate and the pathological complete response (pCR) rates were significantly higher for the TNBC group compared with the non-TNBC group (OR, 2.68; 95% CI, 1.69–6.57; P=0.03 and OR, 2.89; 95% CI, 1.28, 6.53; P= 0.01, respectively). However, in advanced/metastatic breast cancers, the cCR, partial response (PR) and the disease control rates for the TNBC group were not significantly different compared with the non-TNBC group. The 6-month progression-free survival (PFS) rate for the TNBC group was higher than that of the non-TNBC group in all patients (OR, 1.81; 95% CI, 1.11–2.96; P= 0.02). However, the 1- and 2-year PFS rates were not significantly different (OR, 1.42; 95% CI, 0.69–2.92; P=0.35 and OR, 1.11; 95% CI, 0.35–3.52; P= 0.85, respectively). Furthermore, the PFS rates were not significantly different between the groups in patients with advanced/metastatic breast cancer. In conclusion, platinum-based chemotherapy in the breast cancer patients with TNBC showed an improved short-term efficacy compared with the non-TNBC group during neo-adjuvant chemotherapy, but has not yet been demonstrated to have an improved effect in advanced breast cancer.

e13049 Background: COVID-19 pandemic has placed an unprecedented burden on health care system. Patients with cancer are reported to have a higher risk of infection and a more complicated COVID-19 course. Breast cancer (BC) is the most common cancer in women in Turkey. We aimed to evaluate the clinical outcome of breast cancer patients who had a diagnosis of COVID-19. Methods: Medical records of breast cancer patients who had COVID-19 between July 2020-2021 at our center were retrospectively rewieved. We recorded pathological, clinical, treatment characteristics, and the clinical outcome of COVID-19 infection. Results: A total 82 breast cancer (BC) patients had COVID-19 between July 2020-2021. All patients were female, with a median age of 49 (43-64 years). Eighty-five % of all patients had early and 14.6% had advanced stage BC. COVID-19 had a mild clinical course in 73%, hospitalization was required in 27% of patients. Twenty-five patients who required hospitalization were discharged. Three (3,6%) patients who had heavily pretreated metastatic breast cancer, required ICU and died due to COVID-19. Metastatic disease (p 0.002) and chemotherapy within 7 days of COVID-19 diagnosis (p = 0.024) have been associated with increased mortality. Conclusions: In our breast cancer cohort, most patients had a mild COVID-19 course. Advanced disease and chemotherapy within 7 days of diagnosis were the two risk factors for increased mortality.

Simple SummaryImmunotherapy has made tremendous clinical progress in breast cancer. However, in some patients, the response rate to immunotherapy is low because the tumor microenvironment (TME) is highly immunosuppressive and the tumors are not sufficiently immunogenic. Photodynamic therapy (PDT) can not only kill tumor cells directly but also induce immunogenic cell death (ICD), which provides antitumor immunity. This review discusses the recent advances in crosstalk between photodynamic therapy and immunotherapy in breast cancer, aiming to provide new perspectives on the treatment of breast cancer.Breast cancer (BC) is the world’s second most frequent malignancy and the leading cause of mortality among women. All in situ or invasive breast cancer derives from terminal tubulobular units; when the tumor is present only in the ducts or lobules in situ, it is called ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS). The biggest risk factors are age, mutations in breast cancer genes 1 or 2 (BRCA1 or BRCA2), and dense breast tissue. Current treatments are associated with various side effects, recurrence, and poor quality of life. The critical role of the immune system in breast cancer progression/regression should always be considered. Several immunotherapy techniques for BC have been studied, including tumor-targeted antibodies (bispecific antibodies), adoptive T cell therapy, vaccinations, and immune checkpoint inhibition with anti-PD-1 antibodies. In the last decade, significant breakthroughs have been made in breast cancer immunotherapy. This advancement was principally prompted by cancer cells’ escape of immune regulation and the tumor’s subsequent resistance to traditional therapy. Photodynamic therapy (PDT) has shown potential as a cancer treatment. It is less intrusive, more focused, and less damaging to normal cells and tissues. It entails the employment of a photosensitizer (PS) and a specific wavelength of light to create reactive oxygen species. Recently, an increasing number of studies have shown that PDT combined with immunotherapy improves the effect of tumor drugs and reduces tumor immune escape, improving the prognosis of breast cancer patients. Therefore, we objectively evaluate strategies for their limitations and benefits, which are critical to improving outcomes for breast cancer patients. In conclusion, we offer many avenues for further study on tailored immunotherapy, such as oxygen-enhanced PDT and nanoparticles.

Identification of molecular signatures that allow detection of the transition from normal breast epithelial cells to malignant invasive cells is a critical component in the development of diagnostic, therapeutic, and preventative strategies for human breast cancer. Substantial efforts have been devoted to deciphering breast cancer etiology at the genome level, but only a limited number of studies have appeared at the proteome level. In this work, we compared individual in situ proteome profiles of nonpatient matched nine noncancerous, normal breast epithelial (NBE) samples with nine estrogen receptor (ER)-positive (luminal subtype), invasive malignant breast epithelial (MBE) samples by combining laser capture microdissection (LCM) and quantitative shotgun proteomics. A total of 12,970 unique peptides were identified from the 18 samples, and 1623 proteins were selected for quantitative analysis using spectral index (SpI) as a measure of protein abundance. A total of 298 proteins were differentially expressed between NBE and MBE at 95% confidence level, and this differential expression correlated well with immunohistochemistry (IHC) results reported in the Human Protein Atlas (HPA) database. To assess pathway level patterns in the observed expression changes, we developed protein set enrichment analysis (PSEA), a modification of a well-known approach in gene expression analysis, Gene Set Enrichment Analysis (GSEA). Unlike single gene-based functional term enrichment analyses that only examines pathway overrepresentation of proteins above a given significance threshold, PSEA applies a weighted running sum statistic to the entire expression data to discover significantly enriched protein groups. Application of PSEA to the expression data in this study revealed not only well-known ER-dependent and cellular morphology-dependent protein abundance changes, but also significant alterations of downstream targets for multiple transcription factors (TFs), suggesting a role for specific gene regulatory pathways in breast tumorigenesis. A parallel GOMiner analysis revealed both confirmatory and complementary data to PSEA. The combination of the two annotation approaches yielded extensive biological feature mapping for in depth analysis of the quantitative proteomic data.

Our study aimed to compare the efficacy and safety of anthracycline plus taxane (AT)-based neoadjuvant chemotherapy (NAC) with or without cyclophosphamide in the treatment of breast cancer. We searched PubMed, Embase, Web of Science and the Cochrane Library for randomized controlled studies comparing the efficacy and safety of AT-based NAC with or without cyclophosphamide in breast cancer patients. Four eligible studies with 2,302 individuals were ultimately included in the quantitative analysis. After applying the AT-based NAC regimen, the overall rates of pathologic complete response (pCR) and breast conserving surgery in all included subjects were 26.5% and 70.6%, respectively. The rates of pCR [risk ratio (RR): 1.35; 95% CI: 0.75, 2.45; P=0.32], breast-conserving surgery (RR: 1.07; 95% CI: 0.97, 1.19; P=0.17) and clinical response (RR: 1.08; 95% CI: 0.97, 1.19; P=0.15) in patients in the cyclophosphamide group were similar to those in the control group. However, participants in the cyclophosphamide group had a lower no clinical response rate than those in the control group (RR: 0.72; 95% CI: 0.60, 0.87; P<0.001). Subjects in the cyclophosphamide group had significantly lower rates of infection (RR: 0.57; 95% CI: 0.41, 0.79; P<0.001) and diarrhea (RR: 0.46; 95% CI: 0.30, 0.68; P<0.001) and higher rates of thrombocytopenia (RR: 3.38; 95% CI: 1.96, 5.84; P<0.001), sensory/motor neuropathy (RR: 1.57; 95% CI: 1.03, 2.39; P=0.03) and nausea/vomiting (RR: 1.51; 95% CI: 1.11, 2.06; P=0.009) than those in the control group. The AT-based NAC regimen with or without cyclophosphamide had similar clinical outcomes in breast cancer patients. The addition of cyclophosphamide might increase the risks of thrombocytopenia, sensory/motor neuropathy and nausea/vomiting.

Background: Prognostic impact of BRCA1 and BRCA2 mutations in breast cancer has been a subject of several studies over the past few years, with inconsistent interpretations. In an attempt to address this uncertainty, we aimed to study the association between BRCA1/2 mutation carriership and long-term survival outcomes for the first time in Egyptian female breast cancer patients. Patients and Methods: BRCA1/2 mutations were identified in 103 Egyptian female breast cancer patients using HRM analysis and direct sequencing. DNA for genotyping was extracted from whole blood samples submitted at recruitment. Clinicopathological data and long-term outcomes including date and site of disease progression, were retrieved from medical records until death or loss to follow-up. Outcome measures including overall survival (OS), disease-free survival (DFS), locoregional recurrence free survival (LRRFS) and metastasis free survival (MFS) were compared in all BRCA1 or BRCA2 mutation carriers versus non-carriers at 2, 5, 10, and 15 years after diagnosis. Results: Pathogenic variants (Class 5 according to American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines) were observed in 29 cases. The profile of the detected variants was previously reported. Median ages at diagnosis was 40 years (range, 24-57 years) in BRCA carriers and 48 years (range, 39-66 years) in non-carriers (P=0.008). BRCA carriers tended to have early onset breast cancer (48% versus 28%, P=0.05), more likely premenopausal (82% vs 54%, P=0.02), and with positive family history of breast cancer (45% vs 35%, P=0.024). Positive lymph node metastasis was more significantly observed in BRCA carriers (76% vs 53%, P=0.03). After median follow-up time of 6.9 years (range, 4.2-24.4 years), there was no significant difference in OS between BRCA carriers and non-carriers at 10 years: 71.1% [95%CI 51-84] vs 94.3% [84-98]; and at 15 years: 60.2% [38-77] vs 60.4% [43-74]; (P=0.36). No difference was detected in DFS between BRCA carriers versus non-carriers (DFS at 2 years: 83% [95%CI 65-92] vs 88% [76-93]; at 5 years: 34% [18-51] vs 61% [47-72]; and at 10 years: 16% [6-35] vs 35% [21-45]); (P=0.1); or MFS (at 2 years were: 83% [95%CI 65-92] vs 87.7% [76-93]; at 5 years: 38.3% [21-56] vs 62.7% [49-73]; and at 10 years: 17.9% [5-35] vs 38.4% [24-52]; (P=0.2). However, LRRFS was significantly worse in BRCA carriers as compared to non-carriers; at 5 years: 51.1% [28-69] vs 84% [70-92]; and at 10 years: 34.1% [10-40] vs 60.1% [50-75]; (P=0.018). Conclusion: To our knowledge, this is the first study in the Middle East to report the long-term prognostic implications of BRCA1/2 mutations in breast cancer. Though no significant difference was detected in the OS, yet BRCA carriers had high risk of locoregional recurrence and hence, BRCA screening and intensive surveillance should be implemented in the mainstream oncology practice in Egypt. Citation Format: Sherihan Galal AbdelHamid, Hala Osman El-Mesallamy, Hany AbdelAziz, Abdel-Rahman N. zekri. Long-term survival outcomes in Egyptian female breast cancer patients with and without BRCA mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 428.