Zarrar, Raza

Abstract Background The current definition, prognosis, and optimal treatment (tx) for oligometastatic breast cancer (OMBC) are not fully known. With advances in multimodality breast cancer (BC) tx and overall improvement in patient (pt) outcomes, it is important to identify baseline pt factors that confer better prognosis in OMBC and assess the impact of local/regional tx and metastasis (mets)-directed tx on survival outcomes. Methods We reviewed 105 Mayo Clinic pts with OMBC (up to 5 mets) from 2003 to 2021. Pts were excluded from analysis if they were misidentified as having OMBC (n=6), did not have a primary breast mass (n=1), developed de novo BC during tx (n=1), or were lost to follow up (n=2). Categorical variables were summarized as counts. Continuous variables were reported as medians. Kaplan-Meier method was used to estimate survival and the time from diagnosis to next tx at 1, 3, and 5 years. Log-rank test was used to compare survival rates between baseline factors. Univariate Cox proportional hazards models were performed on both baseline and time-dependent factors. All tests were two-sided with p-value < 0.05 considered statistically significant. Results Total pts included were 95. Median age was 49 (range, 26-86), most (93.6%) pts were White, and 46.8% were postmenopausal. Invasive ductal carcinoma (89.5%) was the most common BC type. Median survival was 10.8 years; 1-, 3-, and 5-year survival rates were 98.9%, 87.7%, and 81%, respectively. 58 pts (61.1%) required a change in tx due to disease progression. No significant survival difference was observed in pre- vs. postmenopausal pts (p=0.71) or in groups based on hormone receptor and/or human epidermal growth factor receptor 2 status. 47 pts (49.5%) received local/regional tx; no significant difference in survival (HR 0.57, 95% CI 0.23-1.40; p=0.217) or time to next tx (HR 0.67, 95% CI 0.39-1.15; p=0.144) was seen in this subgroup. Of these pts, 36 (76.6%) received neoadjuvant chemotherapy and/or immunotherapy, 5 of whom (10.6%) also started endocrine tx preoperatively. Overall, 11/47 pts (23.4%) received neoadjuvant endocrine tx. 20 pts received systemic tx without eventual surgery, and 5 pts got palliative radiation (RT). Biopsy-confirmed mets were noted in 76 pts (80%), with bone-only mets in 50%, 30 pts (31.6%) with viscera-only mets and 7 pts (7.4%) with both bone and visceral mets. 18 pts had suspected mets on imaging but did not undergo biopsy. The hazard of death was 6.34 times higher in pts with both bone and visceral mets than those with bone-only mets (p=0.008). Pts with viscera-only mets had higher survival at 2 and 3 years than pts with bone-only or both bone and visceral mets (p=0.093). Pts with 3 mets (7/76, 7.4%) had decreased survival at 1, 2, and 3 years compared to pts with 1-2 (65/76, 85.5%) mets (p=0.6). 67 pts (70.5%) received mets-directed tx; RT alone was the most common modality (52/67, 77.6%), followed by surgery (6/67, 9%), RT plus surgery (5/67, 7.5%), and ablation alone (3/67, 4.5%). There was no significant difference in survival (HR 1.27, 95% CI (0.53, 3.07), p=0.589) or time to next tx (HR 0.95, 95% CI (0.56, 1.63), p=0.856) in pts who received mets-directed tx. Multivariate analysis was not performed because most findings were not statistically significant in univariate analysis. Conclusions We did not find any significant differences in survival based on characteristics like menopausal status or site or number of mets in pts with OMBC. There was a trend toward improved survival in pts with viscera-only mets, but this finding requires validation. Local/regional and mets-directed tx did not improve survival; however, survival at 1, 3, and 5 years was excellent in this OMBC pt population. Our study was limited by low pt numbers and heterogeneity in the pt population. Findings need validation in larger studies. Citation Format: Tanmayi Pai, Raza Zarrar, Zhongwei Peng, Zhuo Li, Lauren Cornell, Kostandinos Sideras, Rohit Rao, Alvaro Moreno-Aspitia, Saranya Chumsri, Sarah McLaughlin, James Jakub, Emmanuel gabriel, Sanjay Bagaria, Laura Vallow, Santo Maimone, Pooja Advani. Clinical Features and Survival Outcomes of Oligometastatic Breast Cancer Patients: The Mayo Clinic Experience [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 PO3-06-04.

Abstract Background Metaplastic breast cancer (MBC) is a rare and aggressive subtype of breast cancer (BC) defined by presence of both epithelial and mesenchymal components. Most are triple negative but are often chemo-refractory and associated with poor survival outcomes compared to non-metaplastic triple negative BC. Advances in therapy have led to improvements in survival outcomes of patients (pts) with BC over the last decade. Our multicenter retrospective study aims to assess (1) progression free survival (PFS) and overall survival (OS) (2) factors predictive of survival outcomes in MBC pts Methods We performed a retrospective analysis of pts diagnosed with MBC from 1997-2021 at Mayo Clinic (Florida, Arizona and Rochester) under IRB approval. Kaplan-Meier method was used to estimate OS and PFS at 1, 3 and 5 years. Cox regression models were used to examine the association between risk factors and survival outcomes. All tests were two-sided with p value < 0.05 considered statistically significant Results We evaluated 158 pts with MBC. Median age and tumor size was 61 (range: 20-91) years and 2.8 (range: 0.5-21) cm, respectively, with 80% of pts being postmenopausal. At diagnosis, 14.6% of pts had clinical T3/T4 disease, 16.4% were clinically node-positive, and 6.3% (10 pts) had distant metastases (DM). Spindle cell histology was seen in 36 pts. Most MBC pts were triple-negative (68.3%), high grade (77.2%) and high Ki-67 (36/47; 76.5%). Of the 61 pts tested for germline mutation, 8 (13.1%) were positive, with BRCA1/2, PTEN, NBN, CHEK2, and BARD1 mutations. Most pts had lumpectomy (53.8%), followed by simple mastectomy (38.5), and modified radical mastectomy (7.7%). Majority of pts had sentinel lymph node biopsy (71.8%). Adjuvant radiation therapy was performed in 65.6% of pts. Pathologic complete response (pCR) was noted in 4/38 (10.5%) evaluable pts who received neoadjuvant chemotherapy (NACT). Residual cancer burden (RCB) scores of 2 and 3 were seen in 76.2% of evaluable pts. Median follow-up time was 2.2 years (range: 6 days-24.6 years). Overall, 1-, 3-, and 5-year OS was 93.3%, 81.7%, and 76.0%, while PFS was 80.8%, 67.9%, and 60.9%, respectively. The presence of DM at diagnosis [HR 38.55 (11.18, 132.93), p < 0.001] and spindle cell histology (SC) [HR 2.57 (1.19, 5.53), p = 0.02] predicted worse OS in multivariable analysis. Inferior PFS was predicted by DM [HR 18.84 (6.53, 54.35), p < 0.001], SC [HR 2.46 (1.25, 4.86), p = 0.009], and node-positivity at diagnosis [HR 3.65 (1.5, 8.89), p = 0.004]. The 5-year OS and PFS were 22.2% and 0% for DM pts versus 80.0% and 65.6% for non-DM pts. The 5-year OS and PFS were 71.5% and 54.7% for SC pts versus 81% and 66.6% for non-SC pts. 5-year OS and PFS for NACT pts was 67.3% and 52.6% for NACT pts versus 78.2% and 62.8% for non-NACT pts. Age at diagnosis, menopausal status, family history of BC, grade, stage, tumor size, hormone-receptor and HER2 status, and use of NACT were not found to be significantly associated with OS or PFS in multivariate analysis. Conclusion This study is one of the largest and most recent review of institutional experiences with MBC. Overall, OS at 5 years was improved compared to prior older studies of MBC but still remains very low for those with DM, representing an area of unmet clinical need. SC and DM correlated with worse outcomes for both PFS and OS. Additionally, node positivity at diagnosis was a predictor of worse PFS. In contrast, no association was seen between survival and tumor size, stage, hormone receptor-positivity, HER2 receptor-positivity. The low pCR rates following NACT in our study are consistent with reported literature. Further, use of NACT does not impact survival, suggesting pts with resectable disease should proceed with surgery first. Citation Format: Siven Chinniah, Raza Zarrar, Zhuo Li, Kostandinos Sideras, Alvaro Moreno-Aspitia, Saranya Chumsri, Rohit Rao, Sarah McLaughlin, James Jakub, Emmanuel Gabriel, Sanjay Bagaria, Laura Vallow, Santo Maimone, Pooja Advani. Clinical Factors associated with Survival Outcomes in Patients with Metaplastic Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-25.