Breast Conservation Therapy vs. Mastectomy Survival in Young Breast Cancer Patients: Systematic Review and Meta-Analysis

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Background Breast cancer is relatively rare in women younger than 35 years of age, accounting for 2–4% of the total number of breast cancer cases diagnosed each year in western countries and the USA 1–3. However, the proportion of young age-onset breast cancer was much higher in the Asian population 3–6. Breast cancer at a young age has been reported to have a more aggressive biological behavior and to be associated with worse prognosis compared with the disease in older patients 5,7–17. Higher incidence of recurrence and risk of death were detected in younger patients, even when more aggressive therapies were administered 10–14. Neoadjuvant chemotherapy (NCT) has been considered the standard treatment for locally advanced breast cancer patients. In human epidermal growth factor receptor 2 (HER2)-positive and triple-negative tumors, achievement of a pathological complete response (pCR) after NCT was associated with better survival outcomes 18. In recent studies, young breast cancer patients were reported to obtain higher pCR rates compared with older counterparts 19,20. However, it remains unclear whether pCR is a predictor for better prognosis in young breast cancer patients. In this study, we aimed to investigate chemotherapy response and its relation with prognosis in young breast cancer patients (<35 years old) who were treated with NCT. Patients and methods Patients From January 2003 to December 2013, patients with operable or locally advanced breast cancer who were treated with NCT at the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College were reviewed systemically. The inclusion criteria for the study were as follows: (i) 35 years or younger or 60 years or older; (ii) diagnosis of invasive carcinoma confirmed by core needle biopsy before NCT and the lymph node status was evaluated by fine needle aspiration of palpable lymph node if applicable; (iii) immunohistochemical examination for estrogen receptor (ER), progesterone receptor (PgR), and HER2 status using tumor specimens from core needle biopsy; (iv) newly diagnosed breast cancer patients; (v) combination of paclitaxel and carboplatin (PC) in patients with triple-negative breast cancer as NCT; for other patients, a combination of cyclophosphamide and epirubincin (CE) as NCT with postoperative paclitaxel, or epirubincin in combination with paclitaxel (ET) as NCT 21; (vi) adequate hematologic, hepatic, and renal functions. The exclusion criteria for the study were as follows: (a) stage IV disease, bilateral breast cancer, male breast cancer, and patients complicated with other malignancies; (b) patients who did not have complete clinical information or immunohistochemistry; (c) patients who were lost to follow-up immediately after treatment. This study was a retrospective observational research and patients' information was collected in the hospital database. There was no direct intervention in patients' treatment or care. Therefore, a patient's consent was not required. This study was approved by the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. Treatment Before the initiation of NCT, bilateral breast MRI or ultrasound, chest radiography, abdominal ultrasound, or computed tomography scans were performed to determine clinical stage. All patients were staged according to the 7th TNM (tumor–node–metastasis) staging system maintained by the American Joint Committee on Cancer (AJCC). All patients received NCT with CE, or ET, or PC regimens. CE-T regimen: cyclophosphamide 600 mg/m2 intravenously, day 1, and epirubicin 80 mg/m2 intravenously, day 1, q14d×4 cycles in NCT, followed by postoperative sequential paclitaxel 175 mg/m2 intravenously, day 1, q14d×4 cycles; ET regimen: epirubincin 75 mg/m2 intravenously, day 1, and paclitaxel 175 mg/m2 intravenously, day 2, q21d×4 cycles as NCT; and two cycles of ET regimen were repeated after surgery; PC regimen: paclitaxel 175 mg/m2 intravenously, day 1, and carboplatin area under the curve=5 intravenously, day 1, q21d×6 cycles as NCT. Mastectomy or breast-conserving surgery was performed within 1 month after the completion of NCT. Adjuvant radiotherapy was prescribed at the discretion of physicians mainly on the basis of the TNM stage before NCT, followed by endocrine therapy in cases with ER-positive or PgR-positive tumors. Trastuzumab was recommended in HER2-positive patients, but not compulsory. Efficacy evaluation Clinical efficacy was estimated every two cycles by clinical, mammographic, B-ultrasound examinations, and MRI according to Response Evaluation Criteria in Solid Tumors 1.1 criteria. Pathological efficacy was assessed by pathologic report after surgery and imaging data. Efficacy evaluation indicators included pCR, clinical complete response (CR), clinical partial response (PR), overall objective response rate (ORR=CR+PR), clinical progressive disease (PD), and clinical stable disease (SD). pCR was defined as no histological evidence of malignancies or only in-situ residuals in breast tissue after surgery, and complete disappearance of lymph node metastasis. CR was defined as disappearance of all known lesions. PR was defined as at least a 30% decrease in the sum of the largest diameters of target lesions. PD was defined as at least a 20% increase in the sum of the largest diameters of target lesions or new lesions detected. SD was defined as a reduction in the largest sum diameters of tumors by no more than 30% or an increase of no more than 20%. Patients with overall objective response rate received planned treatment and sequential surgery. Patients who fulfilled the criteria for SD or PD at the initial efficacy evaluation received surgery as soon as possible and were then treated with alternative postoperative regimens. Statistical analysis All data were analyzed using SPSS medical statistical software (version 15.0; SPSS Inc., Chicago, Illinois, USA). Disease-free survival (DFS) was defined as the period from the date of receiving NCT to the date of recurrence or metastasis or last follow-up; overall survival (OS) was defined as the period from the date of receiving NCT to the date of death for any cause or last follow-up. Both OS and DFS were analyzed using the Kaplan–Meier method. Comparisons of OS or DFS between groups were performed using the log-rank test. A two-tailed P value less than 0.05 was considered statistically significant. The χ2 or Fisher's exact test was performed to compare the clinicopathological variables and pCR rates between the subgroup of younger than 35 years of age and the subgroup of older than 60 years of age. Results Patient characteristics and treatment From January 2003 to December 2013, a total of 141 breast cancer patients were enrolled in this study and 74 (52.5%) of these patients were younger than 35 years old. As shown in Table 1, younger patients presented a tendency to have a tumor size of more than 5 cm (P=0.085), to have axillary positive nodes (P=0.118), and to have lymphovascular invasion (P=0.007) compared with their older counterparts (≥60 years old). As for the treatment, younger patients were more likely to choose breast-conserving surgeries (P=0.024) and to receive adjuvant radiotherapy after surgeries (P<0.001). For the entire cohort, the median number of NCT cycles was 4 (range: 4–6 cycles). The chemotherapy regimens were changed for a total of 31 patients who had a poor response to preoperative chemotherapies (including 26 SD and five PD). Overall, 52% (16/31) of these patients were in the young group, and the other 15 patients were older than 60 years. All 96 patients with preoperative or postoperative pathological ER-positive or PgR-positive breast cancer received different postoperative adjuvant endocrine therapies. In all, 18.9% (14/74) of patients in the young group and 16.4% (11/67) of patients in the old cohort received 1 year of trastuzumab after surgery or adjuvant chemotherapy.Table 1: Patients' baseline characteristicsTreatment response All patients were evaluable for response to NCT. The rates of pCR, clinical PR (except clinical PR, but confirmed as pCR finally), clinical SD, and clinical PD were 12.8% (18/141), 65.2% (92/141), 18.4% (26/141), and 3.5% (5/141), respectively. pCR rates were similar between the young group and the old cohort (12.2 vs. 13.4%, P=0.821). The PC regimen tended to yield higher pCR rates in the young cohort, but this was not statistically significant. HER2-positive or inflammatory breast cancer patients in young group were also more likely to achieve pCR compared with their older counterparts. As shown in Table 2, there were no significant differences between the pCR rates of young and old patients across various subgroup analyses, including hormone receptor status, axillary lymph node metastasis from primary tumors, primary tumor size, HER2 expression status, and NCT regimens.Table 2: Clinical and pathological factors affecting pathological complete response ratesSurvival analysis By the last follow-up on 1 November 2015, with a median follow-up of 32 months, 38 relapse events and 11 deaths have occurred. Patients in the young group showed significantly lower 5-year DFS compared with their old counterparts (Fig. 1a, 62.2 vs. 77.8%, P=0.037). However, no significant difference in 5-year OS was observed between the young group and the old cohorts (Fig. 1b, 84.0 vs. 94.8%, P=0.212).Fig. 1: (a) Kaplan–Meier curves of disease-free survival (DFS) in the young group (N=74) and the elderly group (N=67); Kaplan–Meier curves of overall survival (OS) in the young group (N=74) and the elderly group (N=67).In the group of young patients, pCR was not a significant predictor for DFS (Fig. 2a, P=0.408), whereas significant differences were observed with respect to the ascending TNM stage at diagnosis (Fig. 2b, P=0.001). In the subset of old patients, neither pCR nor TNM stage was a prognostic factor against DFS (Fig. 2c, P=0.129 and Fig. 2d, P=0.174).Fig. 2: Disease-free survival (DFS) curves by chemotherapy response (a) and TNM stage at diagnosis (b) in young patients; DFS curves by chemotherapy response (c) and TNM stage at diagnosis (d) in old patients. pCR, pathological complete response.To further explore the difference in survival between young and old groups, we carried out a stratified analysis. As shown in Fig. 3, the 5-year DFS was lower in the young group than in the old group within the subgroup of patients who presented with inflammatory breast cancer [56.5 vs. 75.1%, hazard ratio (HR)=2.47, P=0.044], with a large primary tumor (46.7 vs. 81.4%, HR=2.93, P=0.053), with lymph node involvement (57.7 vs. 74.8%, HR=2.40, P=0.025), and with higher TNM stage at diagnosis (46.7 vs. 67.1%, HR=2.52, P=0.027). Subgroup analyses on OS were carried out across predefined subsets and no significant difference was observed (Fig. 4).Fig. 3: Forest plot of disease-free survival. Hazard ratio more than 1 indicated that old patients had better survival outcome. CI, confidence interval; ER, estrogen receptor; PgR, progesterone receptor; TNBC, triple-negative breast cancer.Fig. 4: Forest plot of overall survival. Hazard ratio more than 1 indicated that old patients had better survival outcome. CI, confidence interval; ER, estrogen receptor; NA, not available; PgR, progesterone receptor; TNBC, triple-negative breast cancer.Discussion Although there was no consensus definition for young breast cancer, it had been widely believed that breast cancer at a young age had a more aggressive biological behavior compared with the disease arising from older patients. Tumors in younger women present with a higher grade, a higher T stage, a higher N stage, and more dedifferentiation, and have a higher proliferating fraction and more vascular invasion 5,7–17. In our study, the clinicopathological characteristics of young patients were consistent with previous researches. Keegan et al.22 and Colleoni et al. 23 found that higher proportions of HER2-positive tumors occurred in young patients. It was reported that about 25% of all breast cancers are ER or PgR negative, but a large proportion of hormone receptor-negative tumors occur in young women 13,15,17,24. Azim et al. 11 reported that there was a significantly higher proportion of basal-like tumors (34.3%) in young patients compared with those aged 41–52 (27.7%). No significant differences in the breast cancer subtype pattern were observed in this study and this could be attributed to the limited sample size of our study. It has been shown that younger age was associated with a less favorable prognosis 5,7–17. Tang et al. 15 found that with a follow-up of 54 months, inferior 5-year DFS (72 vs. 83%, P<0.01) and 5-year OS (87 vs. 93%, P <0.01) were observed in patients aged younger than 40 years compared with those aged 40–50 years. In our study, worse 5-year DFS was observed in young patients (62.2 vs. 77.8%, P=0.037), which was consistent with the results in previous studies. Stratified analysis showed that the predictive value of age on DFS was proven in the subgroup of patients with high-risk factors, including inflammatory breast cancer, large primary tumor, positive axillary lymph node, or higher TNM tumor stage at diagnosis, whereas no difference in the 5-year DFS was observed in patients without the above-mentioned risk factors. Similarly, in the study of Han et al. 5, there was no significant difference in DFS between young and old groups in lymph node-negative patients (P=0.223), whereas the younger group showed worse prognosis among lymph node-positive patients (P<0.001). In a Korean study, patients in the very young group with lymph node metastasis had poorer 5-year OS (70 vs. 83%, P<0.001) and DFS (58 vs. 74%, P <0.001) than their older counterparts; in patients without lymph node metastasis, the survival outcomes did not differ significantly between the two groups 17. Therefore, it is a key point to identify high-risk young breast cancer patients, and implement a tailored and aggressive treatment to improve the outcomes of these patients. It had been reported that improved survival outcomes were observed in patients with pCR compared with those with residual tumor 18,25–29. Further analysis showed that pCR was associated with better DFS in ER or PgR-positive/HER2-negative with grades 1–2, HER2-positive, and triple-negative disease, but not for those with ER or PgR-positive/HER2-positive, and ER or PgR-positive/HER2-negative with grade 3 tumors 18. In addition, in a meta-regression analysis of 29 heterogeneous neoadjuvant trials, pCR was not suggested to be a surrogate end point for DFS and OS in patients with breast cancer 30. At the 2016 annual meeting of American Society of Clinical Oncology, Robidoux et al. 31 reported 5-year outcomes of the NSABP protocol B-41 and found that long-term outcomes correlated with pCR status. Additional analyses indicated that pCR was related to a significant improvement in survival rates in the ER-negative subset, but not in the ER-positive cohort. In our study, young patients achieving pCR showed similar 5-year DFS compared with those with non-pCR (P=0.408). Therefore, pCR may be not an appropriate surrogate for prognosis in young breast cancer patients treated with NCT. The TNM staging system maintained by the AJCC is considered the most clinically useful cancer staging system for cancers. Orucevic et al. 32 reported on 782 Caucasian women diagnosed with invasive ductal carcinoma who were grouped according to TNM stage and molecular phenotype. The results supported the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes even with the emerging prognostic impact of tumor biomarkers (ER/PgR/HER2). Carey et al.33 suggested that classification of residual tumor in the breast and axillary surgical specimens after NCT using the AJCC TNM staging system could predict distant relapse and survival. In our study, young patients with higher TNM stage at diagnosis showed worse survival outcomes. Therefore, TNM stage may be more predictive of prognosis than pCR in breast cancer patients treated with NCT. This study is limited by its retrospective nature, nonrandomized design, small sample size, and relatively short follow-up duration. Trastuzumab was not covered by medical insurance in China and was much more expensive than common chemotherapy drugs. Therefore, some of the HER2-positive patients could not afford the expense. The diversity of NCT regimens and difference in the proportions of patients receiving trastuzumab between young and old cohorts may also have influenced the results of this study. Further prospective studies are warranted to validate the results. In recent years, researches have confirmed that breast cancer arising in young women is a unique disease entity driven by complex biologic processes extending beyond hormone receptors and hereditary cancer syndromes. Anders et al. 34 found 367 significant gene sets among young women's tumors that specifically distinguished them from tumors arising in older women, including those related to immune function, the mammalian target of rapamycin/rapamycin pathway, hypoxia, BRCA1, stem cells, apoptosis, histone deacetylase, and multiple oncogenic signaling pathways. In the study of Azim et al. 11, breast cancer in the young was enriched with processes related to immature mammary epithelial cells and growth factor signaling. There was also downregulation of apoptosis-related genes. The identification of genomic pathways specific to breast cancer arising in young patients provided a better understanding of the interplay of age and contributing biologic processes and a unique opportunity to explore therapeutic targets. Conclusion Young breast cancer patients treated with NCT present more aggressive clinicopathological features and worse prognosis compared with their elderly counterparts. TNM stage at diagnosis may be more predictive of prognosis than pCR in young breast cancer patients with NCT. The underlying biology of young breast cancer needs to be elucidated and the development of tailored treatment is crucial. Acknowledgements The authors thank all doctors and nurses of the Department of Medical Oncology for their help with the realization of this study. Binghe Xu and Jiayu Wang designed the research, analyzed the data, and wrote the paper; Jingjing Wang analyzed the data and wrote the paper; Jiayu Wang, Qing Li, Pin Zhang, Peng Yuan, Fei Ma, Yang Luo, Ruigang Cai, Ying Fan, Shanshan Chen, Qiao Li, Binghe Xu selected the cases and analyzed the clinical data. Conflicts of interest There are no conflicts of interest.

Comparison of Survival Outcomes in Young Patients With Breast Cancer Receiving Contralateral Prophylactic Mastectomy Versus Unilateral Mastectomy

Objectives and rationale: Breast cancer (BC) arising at a young age is relatively uncommon; however, approximately 6 to 10% of women diagnosed with BC are younger than the age 40. This subgroup of young women presents different risk factors, tumor biology, and clinical outcomes. Moreover, the interpretation of the effects of inherited genetic factors on the prognosis of young patients with BC remains a subject of debate. The primary aim of this study was to evaluate the characteristics of young patients with BC and to compare the long-term oncological results between BRCA-mutation carriers and non-carriers. We retrospectively reviewed all the consecutive young (≤ 40 years old) BC patients treated at the Breast Unit of IRCCS Humanitas Research Hospital (Milan, Italy). All young patients underwent BRCA-mutation analysis. For further analysis young BC patients were divided into two groups: BRCA-mutation carriers versus non-carriers. Tumor, surgical treatment, and post-operative data were compared between the two groups. Primary end-points were: disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). The Kaplan-Meier method was used to generate the recurrence and survival curves. Multivariate analyses were performed using the Cox proportional hazards model to identify independent risk and protective factors for DFS, DDFS, and OS. Results: The characteristics of 63 young BC patients with BRCA-mutation were compared with 339 young BC patients without BRCA-mutation. BRCA-mutation carriers tend to be younger (60.3% versus 34.8% if age ≤ 35 years, odds ratio (OR) = 17.699, 95% confidence interval (95%CI) = 33.871-35.568, p = 0.001) and present more aggressive tumors (66.7% versus 40.7% if G3, OR = 17.119, 95%CI = 2.549-2.828, p = 0.001; 57.2% versus 12.4% if biological subtype triple negative, OR = 52.727, 95%CI = 2.042-2.417, p = 0.001; 73.0% versus 39.2% if Ki67 ≥ 25%, OR = 58.981, 95%CI = 47.135-58.505, p = 0.001). Young BC patients without BRCA-mutation presented significantly better long-term oncological results in terms of DFS, DDFS, and OS compared with young BRCA-mutation carriers (10-years DFS rate 91.1% versus 58.1%, p &amp;lt; 0.001; 10-year DDFS rate 91.2% versus 76.1%, p = 0.003; 10-year OS rate 98.0% versus 87.8%, p = 0.002, respectively). Neo-adjuvant chemotherapy was found to be an independent protective factor for OS in young BRCA-mutated BC patients (hazard radio = 14.885, 95%CI = 2.343-94.566, p = 0.004). Conclusions: Breast cancer is more likely to present at a younger age (≤ 35 years) and with more aggressive characteristics (G3, triple negative, Ki67 ≥ 25%) in patients with BRCA-mutation compared with their non-mutated counterpart. Young BRCA-mutation carriers show a poorer prognosis in terms of recurrence and survival compared with non-carriers. The implementation of neo-adjuvant chemotherapy may improve survival in young BC patients with BRCA-mutation. Citation Format: Damiano Gentile, Simone Di Maria Grimaldi, Andrea Sagona, Erika Barbieri, Alberto Bottini, Giuseppe Canavese, Giulia Caraceni, Shadya Darwish, Corrado Tinterri. Comparison of long-term oncological outcomes in young women with breast cancer between BRCA-mutation carriers versus non-carriers: How genetic risk factors and tumor characteristics influence the prognosis [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 PO5-22-08.

BackgroundThe prognosis of multifocal multicentric breast cancer (MIBC) was related to many factors, and there are different recommendations for surgical approaches. We compare the effects of breast-conserving surgery (BCS) and mastectomy on the survival of multifocal multicenter breast cancer female patients.MethodsA total of 38,164 female patients with pathologically confirmed multifocal multicenter invasive breast cancer from 2000 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database were extracted, and the effects of different factors on the survival of these patients were retrospectively analyzed. The patients were divided into a BCS group and a mastectomy group, and the differences of breast cancer-specific survival (BCSS) and overall survival (OS) were compared between the 2 groups.ResultsOf the 38,164 patients included in the analysis, 14,533 (38.08%) underwent BCS and 23,631 (61.92%) underwent mastectomy. Multivariate analysis showed that age, grading, staging, number of lesions, radiotherapy, and BCS would affect the independent factors of BCSS and OS in patients. The median follow-up time was 108 months [interquartile range (IQR): 64–162 months). Multifactorial Cox proportional model analysis of prognostic risk showed that BCS reduced BCSS in patients older than 70 years [hazard ratio (HR): 1.35; 95% confidence interval (CI): 1.2–1.53; P<0.001], stage I and II, positive hormone receptor (HR), all 2–3 lesions, no radiotherapy (HR: 1.46; 95% CI: 1.33–1.6; P<0.001) and no chemotherapy (HR: 1.42; 95% CI: 1.28–1.57; P<0.001); BCS also reduced OS in patients over 40 years of age, stages I, II, and IIIC, all molecular subtypes, all HR-positive or negative, 2–3 lesions, and no radiotherapy (HR: 1.38; 95% CI: 1.31–1.46; P<0.001) and no chemotherapy (HR: 1.36; 95% CI: 1.29–1.44; P<0.001) patients. Multivariate Cox regression showed that BCS is an adverse factor for BCSS [adjusted HR 1.2 (1.11–1.3), P<0.001] and OS [adjusted HR 1.24 (1.19–1.3), P<0.001].ConclusionsIn early, good prognosis, treatment-sensitive patients, there is no survival advantage for BCS and more BCSS and OS benefit for mastectomy patients.

Background: Recent clinical trials comparing local recurrence rates in young breast cancer (BC) patients after breast-conserving therapy (BCT) versus mastectomy are limited. The local recurrence (LR) rate in young BC patients is notably higher than in other age groups, whether the recurrence rates after the two surgical options are comparable remains unclear. This meta-analysis aimed to assess the safety of BCT and mastectomy for young age BC patients by comparing LR rates between the two procedures. Methods: We conducted a systematic search of four electronic databases (Medline, PubMed, Cochrane Library, and Web of Science) for relevant studies comparing LR rates in BC patients aged 40 years or younger who were treated with BCT or mastectomy. Studies that met the inclusion criteria were synthesized using a random-effects model, with a primary focus on LR rates. Sensitivity analyses and meta-regression were performed to evaluate bias and heterogeneity, ensuring a thorough assessment of the available evidence. Results: Among the 2,936 studies screened, 10 studies encompassing 9,215 patients were included, with 5,236 undergoing BCT and 5,803 undergoing mastectomy. The summary odds ratio (OR) indicated a significantly greater risk of LR for BCT compared to mastectomy among young BC patients (OR = 1.48; 95% CI: 1.12–1.96). In subgroup analysis, the BCT group exhibited a higher 5-year LR rate (OR = 1.67; 95% CI: 1.13–2.46) compared to the mastectomy group. This trend persisted across tumor stages, with the BCT group showing an increased LR risk in both the T1–2 (OR = 1.84; 95% CI: 1.44–2.36) and T1–4 (OR = 1.74, 95% CI: 1.50–2.03) stages. Nodal status analysis indicated a higher LR risk for BCT in the N0–1 (OR = 2.549, 95% CI: 1.79–3.46) stages. Among very young women (aged ≤35), the difference in LR rates between BCT and mastectomy was even more pronounced (OR = 2.04, 95% CI: 1.47–2.82). Conclusion: Our meta-analysis found that young BC patients undergoing BCT had a significantly higher risk of LR, with a 48% increased risk compared to those who underwent mastectomy (OR = 1.48; 95% CI: 1.12–1.96). This difference was even more pronounced in patients aged 35 years or younger. While the elevated LR risk with BCT in young patients is well documented, individualized treatment planning should weigh this against potential survival advantages and quality-of-life preservation.

Breast-conserving therapy was once a contraindication in young breast cancer patients (aged ≤40 years). Emerging studies suggest that breast-conserving therapy and mastectomy could achieve similar prognosis in this population. However, the effect of molecular subtype disparity on surgical strategy in these patients remains unclear. Data from 8656 young patients (aged ≤40 years) diagnosed with invasive breast cancer between in 2010 and 2014 were retrospectively reviewed from the Surveillance, Epidemiology, and End Results database. The Cox proportional hazards model was used to evaluate subtype-dependent relationships between the surgical method and survival. Of the 8656 patients, 4132 (47.7%) underwent breast-conserving therapy and 4524 (52.3%) underwent mastectomy. The median follow-up period was 30.0 months. Patients in the breast-conserving therapy group demonstrated better overall survival and breast cancer-specific survival than those in the mastectomy group (both p < 0.05). Patients with different molecular subtypes exhibited significant differences in overall survival and breast cancer-specific survival (p < 0.001). Patients with luminal subtypes experienced better overall survival and breast cancer-specific survival than those with the triple-negative subtype. Multivariate analysis revealed that overall mortality risk of the breast-conserving therapy group was lower than that of the mastectomy group among HR(+)HER-2(-) and HR(-)HER-2(-) patients (overall mortality risk of 36.3% [adjusted hazard ratio = 0.637 {95% confidence interval = 0.448–0.905}, p = 0.012] and 36.0% [adjusted hazard ratio = 0.640 {95% confidence interval = 0.455–0.901}, p = 0.010] respectively.) The breast cancer-specific mortality risk was also lower by a percentage similar to that of the overall mortality risk. In the HR(+)HER-2(+) group, the surgical method was an independent prognostic factor for breast cancer-specific survival (adjusted hazard ratio = 0.275 [95% confidence interval = 0.089–0.849], p = 0.025), while there was a trend that patients with breast-conserving therapy had better overall survival than those with mastectomy (p = 0.056). In the HR(-)HER-2(+) group, no significant difference was observed in overall survival and breast cancer-specific survival (p = 0.791 and p = 0.262, respectively). Breast-conserving therapy resulted in significantly better prognosis in patients with luminal and triple-negative subtypes, while no significant difference was observed in patients with the HER-2 enriched subtype. These results may be helpful in informing clinically precise decision-making for surgery in this population.

To assess clinical and surgical factors affecting local recurrence and survival in young breast cancer patients in the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH). Emerging data suggest young age is a predictor of increased local recurrence. POSH is a prospective cohort of 3024 women of 18 to 40 years with breast cancer. Cohort characteristics were grouped by mastectomy or BCS. Endpoints were local-recurrence interval (LRI), distant disease-free interval (DDFI), and overall survival (OS); described using cumulative-hazard and Kaplan-Meier plots and multivariable analyses by Flexible Parametric and Cox regression models. Mastectomy was performed in 1464 patients and breast-conserving surgery (BCS) in 1395. Patients undergoing mastectomy had larger tumors and higher proportions of positive family history, estrogen receptor+, progesterone receptor+, and/or human epidermal growth factor receptor 2+ tumors. Local events accounted for 15% of recurrences. LRI by surgical type varied over time with LRI similar at 18 months (1.0% vs 1.0%, P = 0.348) but higher for BCS at 5 and 10 years (5.3% vs 2.6%, P < 0.001; and 11.7% vs 4.9%, P < 0.001, respectively). Similar results were found in the adjusted model. Conversely, distant-metastases and deaths were lower for BCS but not after adjusting for prognostic factors. After mastectomy chest-wall radiotherapy was associated with improved LRI (hazard ratio, HR = 0.46, P = 0.015). Positive surgical margins, and development of local recurrence predicted for reduced DDFI (HR = 0.50, P < 0.001; and HR = 0.29, P = 0.001, respectively). Surgical extent appears less important for DDFI than completeness of excision or, where appropriate, chest-wall radiotherapy. Despite higher local-recurrence rates for BCS, surgical type does not influence DDFI or OS after adjusting for known prognostic factors in young breast cancer patients.

Background: This study aims to evaluate the overall and breast cancer-specific survival (BCSS) after breast-conserving surgery (BCS) plus radiotherapy (RT) compared with mastectomy plus RT in resectable breast cancer. Moreover, the aim is to also identify the subgroups who benefit from BCS plus RT and establish a predictive nomogram for stage II patients. Methods: Stage I–III breast cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 1990 and 2016. Patients with available clinical information were split into two groups: BCS plus RT and mastectomy plus RT. Kaplan–Meier survival analysis, univariate and multivariate regression analysis, and propensity score matching were used in the study. Hazard ratio (HR) was calculated based on stratified Cox univariate regression analyses. A prognostic nomogram by multivariable Cox regression model was developed for stage II patients, and consistency index (C-index) and calibration curve were used to evaluate the accuracy of the nomogram in the training and validation set. Results: A total of 24,590 eligible patients were enrolled. The difference in overall survival (OS) and BCSS remained significant in stage II patients both before and after PSM (after PSM: OS: HR = 0.8536, p = 0.0115; BCSS: HR = 0.7803, p = 0.0013). In stage II patients, the survival advantage effect of BCS plus RT on OS and BCSS was observed in the following subgroups: any age, smaller tumor size (<1 cm), stage IIA (T2N0, T0–1N1), ER (+), and any PR status. Secondly, the C-indexes for BCSS prediction was 0.714 (95% CI 0.694–0.734). The calibration curves showed perfect agreement in both the training and validation sets. Conclusions: BCS plus RT significantly improved the survival rates for patients of stage IIA (T2N0, T0–1N1), ER (+). For stage II patients, the nomogram was a good predictor of 5-, 10-, and 15-year BCSS. Our study may help guide treatment decisions and prolong the survival of stage II breast cancer patients.

Introduction: Patients with triple-negative (TN) or HER2-enriched ipsilateral breast cancer recurrence (IBCR) seem to be excluded from a second breast-conserving surgery (BCS) under the assumption that salvage mastectomy would provide better oncological outcomes. Objectives: The objective of this study was to describe the clinical features of these patients, to compare the two surgical alternatives (salvage mastectomy versus second BCS) in terms of oncological results, and to identify independent factors influencing prognosis and surgical treatment. Methods: We retrospectively reviewed all the consecutive patients with histologically confirmed TN or HER2-enriched IBCR. Disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed and compared between the two groups. Results: Eighty-five patients were affected by TN or HER2-enriched IBCR, with a median age of 60 years (range, 32-87 years). The majority of patients (72.9%) were treated with salvage mastectomy. There was no significant difference in terms of DFS between patients receiving a second BCS or mastectomy (p=0.596). However, patients undergoing a second BCS had significantly better DDFS, OS, and BCSS compared to mastectomy (p=0.009; p=0.002; p=0.001, respectively). Tumor dimension &amp;lt; 16 mm (78.3% versus 38.7%, hazard ratio (HR)=3.602, 95% confidence interval (95% CI)=1.534-8.459, p=0.003) was found to significantly increase the probability of receiving a second BCS and positively affects recurrence and survival outcomes (DFS: HR=8.065, 95% CI=2.320-28.034, p=0.001; DDFS: HR=17.011, 95% CI=3.853-75.099, p=0.001; OS: HR: 13.881, 95% CI=2.730-70.579, p=0.002; BCSS: HR=36.773, 95% CI=4.579-295.322, p=0.001). Second BCS represents an independent protective factor for OS and BCSS (OS: HR=0.246, 95% CI=0.027-0.697, p=0.002; BCSS: HR=0.313, 95% CI=0.092-0.511, p=0.002). Conclusion: Salvage mastectomy is not always necessary and it does not seem to increase survival compared to a second BCS. This reinforces the concept that the prognosis of TN and HER2-enriched BC recurrence is mainly driven by the biology of the disease, rather than by the extent of surgery. In patients with small (&amp;lt; 16 mm) aggressive subtypes of IBCR, a second conservative approach can still be evaluated and offered, presenting acceptable loco-regional control and survival. Citation Format: Damiano Gentile, Andrea Sagona, Erika Barbieri, Simone Di Maria Grimaldi, Ruggero Spoto, Davide Franceschini, Stefano Vaccari, Valeriano Vinci, Ersilia Biondi, Lorenzo Scardina, Corrado Tinterri. Salvage mastectomy is not always necessary for aggressive subtypes of ipsilateral breast cancer recurrence: A single-institution retrospective study [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 P1-09-09.

Background: Recent clinical trials comparing local recurrence rates in young breast cancer(BC) patients after breast-conserving therapy (BCT) vs. mastectomy are scarce. This meta-analysis aims to determine the optimal surgical approach for this group by assessing local recurrence (LR) rates between BCT and mastectomy. Methods: We systematically searched four electronic databases (Medline, PubMed, Cochrane Library, and Web of Science) for relevant studies comparing LR rates in BC patients ≤40 years old treated with BCT plus radiotherapy or mastectomy. Studies meeting the inclusion criteria were synthesized using a random-effects model, with a focus on LR rates. We conducted sensitivity analyses and meta-regression to assess publication bias and heterogeneity, ensuring a rigorous evaluation of the available evidence. Results: Out of 485 screened citations, 11 studies encompassing 9215 patients were included, with 4190 undergoing BCT and 5025 undergoing mastectomy. The summary OR revealed a significantly higher risk of LR for BCT compared to mastectomy among young breast cancer patients (OR = 1.63; 95% CI: 1.25-2.13). Specifically, the BCT group exhibited a higher 5-year LR rate (OR = 1.86, 95% CI: 1.13-2.62) and a 5-10-year LR rate (OR = 1.50, 95% CI: 1.00-2.25) compared to the mastectomy group. This trend held true across tumor stages, with the BCT group showing increased LR risk for both T1-2 (OR = 1.88, 95% CI: 1.20-2.94) and T1-4 (OR = 1.46, 95% CI: 1.02-2.10) stages. Similarly, nodal status analysis indicated a higher LR risk for BCT in N0-1 (OR = 2.56, 95% CI: 1.90-3.44) and N0-3 (OR = 1.38, 95% CI: 0.99-1.93) stages. Notably, among very young women (age ≤ 35), the difference in LR rate between BCT and mastectomy was pronounced (OR = 2.04, 95% CI: 1.48-2.81). Overall, for breast cancer patients aged ≤ 40 years, the BCT group consistently demonstrated a higher risk of LR compared to the mastectomy group (OR = 1.53, 95% CI: 1.10-2.13). Conclusion: Our meta-analysis revealed that among young breast cancer patients, BCT was associated with a significantly elevated risk of LR compared to mastectomy, particularly in those ≤35 years old. This heightened risk persisted across various tumor and nodal stages. For very young breast cancer patients, a comprehensive consideration of surgical options is warranted, with caution exercised in selecting BCT. While overall survival (OS) rates were comparable between the two groups in young women, further research is warranted to elucidate these findings and guide clinical decision-making. [1-3]

Background: BRCA mutated breast cancer is associated with an aggressive phenotype with marked differences in histological grade and distant metastases and sensitive to PARPi and platinum therapy. Studies evaluating role of BRCA mutations on the survival outcomes in breast cancer (BC) patients have given confounding results due to the differences in clinical and pathological status among study population. Therefore, we assessed the impact of BRCA mutations on survival of BC patients, based on their baseline characteristics and follow-up durations. Methods: Using PICO framework, articles comparing survival outcomes of BC patients having BRCA mutations against sporadic BRCA phenotype were retrieved from PubMed, EMBASE and Cochrane Library. Overall survival (OS) was the primary outcome, with disease free survival (DFS), distant metastasis free survival (DMFS) and breast cancer specific survival (BCCS) as the secondary outcomes. Hazard ratio (HR) with 95% confidence interval (CI) was used for analysis. Sub-group analysis was performed for survival based on age, tumor stage, estrogen receptor status, triple negative breast cancer (TNBC) status, tumor stage (Stage I-III vs I-IV) and follow-up durations. Results: Altogether, 30 articles with 35,972 patients (mean age 45.6 years) were included in the analysis. In BRCA1/2+ group, no significant difference in OS and DFS than BRCA- group were observed (HR: 0.98, 1.36, respectively),have a better DMFS in BRCA- patients than that in BRCA1/2+ patients (HR: 1.32; 95% CI: 0.71, 2.44). However, the difference observed between the groups was insignificant (P = 0.3825). BRCA1+ patients had significantly lower OS (HR [95%CI]: 1.2 [1.08, 1.33]; P&amp;lt;0.001),poor BCSS at 10 years follow-up. DMFS was significantly poor in BRCA1+ patients compared with BRCA- patients both at 5 years follow-up (HR [95%CI]: 1.07 [1.04, 1.10]; P&amp;lt;0.0001) and 10 years follow-up (HR [95%CI]: 1.21 [1.13, 1.29]; P&amp;lt;0.0001).BRCA2+ patients had significantly lower DFS (HR [95%CI]: 1.35 [1.1, 1.67]; P = 0.0049) and BCSS (HR [95%CI]: 1.46 [1.26, 1.7]; P&amp;lt;0.0001) than BRCA2- patients. Among TNBC patients, OS was non-significantly better in BRCA1/2+ patients (HR 0.96, P = 0.803) than in BRCA- patients. However, DFS was significantly poor in BRCA1+ TNBC patients than BRCA1-/TNBC patients (HR [95% CI]:1.65 [1.08, 2.54]; P = 0.0216).Conclusion: BRCA1/2 mutation is associated with poor prognosis in patient with breast cancer. Hence, BRCA testing might help assess patient prognosis and treatment such as PARPi and platinum. Citation Format: Miao Liu, Shu Wang. Association between BRCA mutational status and survival in patients with breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-51.

Background: Breast cancer is a severe public health problem for women worldwide. Race disparities and regional disparities are documented regarding incidence, mortality, and survival of breast cancer patients. However, the associations between socioeconomic status and survival outcomes of breast cancer remain unclear and require a comprehensive large-scale investigation of specific socioeconomic factors. Furthermore, no model has included both histological and socioeconomic factors together to predict survival of breast cancer. In this study, we sought to develop nomograms to predict overall survival (OS) and breast cancer-specific survival (BCSS) with consideration of socioeconomic factors for non-metastasis breast cancer. Methods: We included a total of 274,108 female patients, diagnosed with malignant breast cancer between 2007 and 2014from the Surveillance, Epidemiology, and End Results (SEER) database. Socioeconomic factors involving marital status, insurance status, residence, median household income, poverty rate, unemployment rate and education level were included in the analysis. OS and BCSS were evaluated with log-rank tests and Kaplan-Meier estimates. We identified and integrated significant prognostic factors for OS and BCSS using univariate and multivariate Cox regression analysis to construct nomograms. Calibration plots and concordance indexes were used to evaluate the accuracy and discrimination of the models. Results: Among different age subgroups, insured patients were more likely to have better survival than uninsured patients or patients with Medicaid (P&amp;lt;0.001), and especially for patients who were aged 18 to 35 years old at diagnosis, uninsured patients associated with poor BCSS than Medicaid patients (P&amp;lt;0.05). Through multivariate analysis, we found non-Hispanic black patients experienced worst survival compared with the White and other races (P&amp;lt;0.001). Interestingly, married (vs. single vs. separated/divorced/widowed; P&amp;lt;0.001) and insured (vs. Medicaid vs. uninsured; P&amp;lt;0.001) patients had a better prognosis. Living in the non-metro area increased the risk of death (hazard ratio [HR], 1.084, P&amp;lt;0.05). Furthermore, living in counties with higher median household income (&amp;gt;US $72,800) had favorable impacts on OS (HR 0.843, P&amp;lt;0.001). Four and five socioeconomic factors were involved in constructing the nomograms for 3 years-, 5 years- and 7 years- OS and BCSS, respectively. The C-indexes of the final nomograms were higher than those of the TNM staging system for predicting OS (0.776 vs 0.678; P &amp;lt; 0.001) and BCSS (0.842 vs 0.776; P &amp;lt; 0.001), respectively. The performance of the nomograms for predicting OS was significantly lower when excluding the socioeconomic factors (P &amp;lt; 0.001). Conclusion: Some certain socioeconomic factors (i.e., marital status, insurance status, median household income, and residence) play essential roles in predicting survival of non-metastasis breast cancer. We constructed and validated nomograms including socioeconomic factors to provide more comprehensive and realistic survival estimation. Besides, these findings may highlight the importance of developing health-related policies and the necessity of targeted social support-based interventions for those high-risk patients. Citation Format: Ji P, Gong Y, Hu X, Hong D, Shao Z-M. Association between socioeconomic factors at diagnosis and survival in non-metastatic breast cancer: A population-based study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-09-09.

INTRODUCTION In breast cancer (BC) patients, achieving a complete pathological response (pCR) after neoadjuvant chemotherapy (NCT) is associated with better prognosis. Despite this, some of these patients will experience recurrences of the disease and will eventually die of BC. We identified clinical factors that can affect recurrence and survival in BC patients who achieve pCR.METHODSRetrospective analysis of a Chilean BC database including patients treated in public and private hospitals in Santiago, Chile from 2010 to 2019. pCR was defined as the absence of residual invasive disease in the breast and in the axillary lymph nodes (ypT0/is N0) at the completion of the NCT. Invasive Disease-Free Survival (IDFS), Distant Disease-Free Survival (DDFS) and BC-specific survival (BCS) was measured from the time of diagnosis to the event or lost to follow-up. We performed Cox regression analysis to identify factors associated with prognosis.RESULTSFrom 855 patients who received NCT, 195 (22.8%) achieved pCR and were included in this study. Clinical characteristics are shown in table 1. 76 (37.9%) patients had hormone receptor positive (HR+) and 113 (57.4%) had Human epidermal growth factor 2 (HER2) positive tumors. 88.7% were treated with a regimen that included anthracyclines and taxanes. With a median follow-up of 36 months, three-year IDFS, DDFS and BCS and their 95% confidence intervals were 90.9% (84.7 - 94.6), 91.8% (86.0 - 95.3) and 93.8% (87.8 - 97.5); respectively. The stage at diagnosis was the only predictor associated with IDFS (Hazard ratio (HR) = 5.6; p = 0.02), DDFS (HR = 4.1, p = 0.07), and BCS (HR = 8.3, p = 0.04). Body mass index (BMI), age, hospital, HR or HER2 status, lymph node involvement, or the presence of an in-situ component, were not associated with prognosis in the multivariate analysis.CONCLUSIONThe clinical stage at diagnosis was the only predictor of survival in patients who achieved pCR after NCT. Short follow-up and few events may have affected these results. This data is consistent with previously published work. Table 1. Tumor and patient characteristicsMedian age49 (24 – 78)HospitalPublic57.4%Private43.6%BMIMedian27.2 (18.5 – 44.7)Overweight38.0%Obese31.9%Receptor StatusRH+/HER2-16.4%RH+/HER2+21.5%RH-/HER2+35.9%RH-/HER2-26.2%Clinical StageI2.1%II47.4%III50.5%Lymph Node +69.7%ypT0/N078.1%ChemotherapyAnthracycline5.1%Taxane6.2%Anthracycline-Taxane88.7% Citation Format: Francisco Acevedo, Benjamin Walbaum, Tomas Merino, Militza Petric, Cesar Sanchez. Clinical stage is the only predictor of survival in breast cancer patients with a complete pathological response [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-37.

Recent cohort studies demonstrated better overall survival (OS) or breast cancer-specific survival (BCS) for breast-conserving therapy (BCT) followed by radiation (RT) compared to mastectomy alone (MT). This is the first observational study in which adjustments for a comprehensive set of prognostic factors, adjuvant therapies, mode of detection, and comorbidities were possible to investigate OS, BCS, as well as recurrence risk of patients undergoing BCT + RT, MT + RT, or MT. Women aged 50-74years at diagnosis of early-stage invasive breast cancer (I-IIIa) between 2001 and 2005 at the German population-based case-control study (MARIE study) were recruited and followed prospectively as a case cohort until 2015. Kaplan-Meier estimates and stepwise adjusted multivariable Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). The 2762 patients included were followed up for a median of 11.9years (95% CI 11.8-12.0). 74.2% of patients underwent BCT + RT; 10.3% MT + RT and 15.6% MT alone. Compared to patients treated with MT alone, patients treated with BCT + RT showed non-statistically significant improved OS (HR 0.79, 95% CI 0.61-1.02), BCS (HR 0.79, 95% CI 0.55-1.12), and no difference in recurrence risks (HR 1.01, 95% CI 0.74-1.37). For patients treated with MT + RT, there were no differences in OS (HR 1.06, 95% CI 0.75-1.50), BCS (HR 1.17, 95% CI 0.75-1.82), or recurrence risk (HR 1.33, 95% CI 0.89-1.97). Among patients with early-stage breast cancer, clinical outcomes more than 10years after diagnosis did not differ between the primary treatment options BCT + RT, MT + RT versus MT alone after full adjustment.