5-year Breast Cancer-specific Survival Research Articles

Abstract PS7-39: Survival differences in chinese versus white women with breast cancer in the United States: A SEER-based analysis

Abstract Purpose: Several studies have reported lower breast cancer survival rates among Black women compared to White women, but less is known regarding outcomes in Chinese women. We compared survival rates for Chinese and White women with breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed between 2004 and 2015. Methods: We conducted a cohort study of Chinese and White women with breast cancer diagnosed between 2004 to 2015 in the SEER18 registries database. We abstracted information on age and year of diagnosis, marital status, median household income, tumour size and grade, lymph node status, clinical stage, receptor status (estrogen, progesterone, and HER-2/neu receptor), surgical treatment (lumpectomy versus mastectomy), receipt of radiotherapy and chemotherapy, and death. Chinese and White women were compared for demographic, pathologic and treatment variables and differences were assessed using standardized differences. Our primary outcome was death from breast cancer. We compared crude breast cancer-specific mortality rates between the two ethnic groups. We also calculated adjusted hazard ratios (HR) in a propensity-matched design using the Cox proportional hazards model. Women were matched on the year of diagnosis and age at diagnosis (both within 2 years), tumour grade, nodal status, clinical stage, estrogen receptor status, HER2/neu status and propensity score. The propensity score accounted for marital status, household income, tumour size, progesterone receptor status and surgical procedure. A log-rank test was used to compare differences between groups using the Kaplan-Meier method. P values < .05 were considered statistically significant. Results: There were 7,553 Chinese women (1.8%) and 414,618 White women (98.2%) with stage I-IV breast cancer registered in the SEER database. There were only small differences in tumour size, stage at presentation, node-positivity, the proportion of HER2-positive cancers, and the treatments received. Among women with stage I-IIIC breast cancer, 10-year breast cancer-specific survival was 88.8% for Chinese women, compared with 85.6% for White women. The cumulative mortality from breast cancer after 11 years of follow-up was 12.9% for Chinese women and 16.4% for White women; crude HR 0.73 (95% CI 0.67 - 0.80; P < .0001). In the first nine years after diagnosis, annual mortality rates are higher in White women than for Chinese women. Following the first nine years after diagnosis, the annual mortality rate for Chinese women then exceeds that of White women. In a propensity-matched analysis, the cumulative mortality from breast cancer after 11 years of follow-up was 8.9% for Chinese women and 11.9% for White women (P = .0002). The adjusted hazard ratio was 0.71 (95% CI 0.62 - 0.81) and was similar to the crude hazard ratio of 0.73 (95% CI 0.67 - 0.90). The adjusted hazard ratios demonstrate that Chinese women had better survival than White women in subgroups defined by age of diagnosis, tumour size and grade, clinical stage, nodal status and estrogen receptor status. The largest effects were observed for stage I cancers (HR 0.57, 95% CI 0.36-0.90) and for node-negative cancers (HR 0.61, 95% CI 0.46-0.82). Conclusion: Chinese women diagnosed with breast cancer in the SEER database between 2004 to 2015 had significantly better survival rates than White women with breast cancer. Over a 10-year follow-up period, Chinese women with stage I-IIIC breast cancer experienced a 30% lower risk of death than a comparable group of White women with breast cancer. The observed difference cannot be accounted for by clinical presentation or by differences in treatment and suggests that there are intrinsic biological differences in breast cancer between Chinese and White women. Citation Format: David Wai Lim, Vasily Giannakeas, Steven A Narod. Survival differences in chinese versus white women with breast cancer in the United States: A SEER-based analysis [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 PS7-39.

Abstract PS6-51: Identification of a low-risk luminal breast cancer cohort that may not benefit from multi-gene testing

Abstract Purpose: Dutch clinical risk criteria (low-risk definition: age > 35 years and (grade 1 with tumor ≤3cm, grade 2 with tumor ≤2cm, or grade 3 with tumor ≤1cm) have been used to stratify the benefit of MammaPrint and Oncotype DX for the decision-making regarding adjuvant chemotherapy for early-stage luminal breast cancer. We propose that the criteria could help to identify low-risk patients who could barely benefit from multi-gene testing. Materials and methods: Breast cancer patients from Taiwan Cancer Database initially treated with primary surgeries between 2008 and 2012 who met the following criteria: (1) pathologic node-negative, (2) hormone receptor-positive, (3) HER2-negative, (4) undergone hormonal therapy, and (5) a minimum follow-up time of 5-year if free from any event, were enrolled in this study. Out of the total 2679 eligible patients, 1074 (40.1%) patients received adjuvant chemotherapy in addition to endocrine therapy. The study endpoints included breast cancer-specific survival (BCSS) and overall survival (OS). Kaplan-Meier statistics estimated the difference between clinical outcomes in low- and high-risk groups. Results: The median follow-up time of BSCC and OS was 5.9 years (range, 0-7 years) and 5.8 years (range, 0-7 years), respectively. There were statistical significances of 5-year BCSS (n=2679) and 5-year OS (n=2636) between low-risk and high-risk groups (in both endpoints, P < 0.0001). According to the Dutch criteria, low-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 99.0% vs. 99.2% and a 5-year OS of 98.4% vs. 97.4%, respectively. High-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 97.7% vs. 98.1% and a 5-year OS of 96.4% vs. 95.3%, respectively. Conclusion: The benefit of chemotherapy in low-risk patients classified by Dutch criteria might be very small since the breast cancer mortality was less than 1% with a minimum of 5-year follow-up. Dutch criteria cannot identify high-risk patients who would benefit from chemotherapy. We assumed that multi-gene testing in low-risk patients would not be cost-effective. Citation Format: Lei Lei, Han-Ching Chan, Tzu-Pin Lu, Xian-Yuan Miao, Zi-Yan Yang, Jia-Huan Huang, Xiao-Jia Wang, Hung-Chun Skye Cheng. Identification of a low-risk luminal breast cancer cohort that may not benefit from multi-gene testing [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 PS6-51.

Additional radiotherapy to breast-conserving surgery is an optional treatment for de novo stage IV breast cancer: A population-based analysis.

BackgroundWe aim to assess the value of locoregional treatment (LRT) including breast‐conserving surgery (BCS), mastectomy (MAST), and radiotherapy (RT) in patients with de novo stage IV breast cancer.MethodsPatients with de novo stage IV breast cancer were retrospectively identified from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. Kaplan‐Meier analysis, log‐rank tests, propensity score matching (PSM), and the multivariate Cox proportional model were used for statistical analysis.ResultsA total of 5798 patients were identified including 849 (14.6%), 763 (13.2%), 2338 (40.3%), and 1848 (31.9%) who received BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively. The proportions of receiving BCS decreased from 35.9% in 2004 to 26.2% in 2014 (p = 0.002), and the probability of patients receiving MAST increased from 64.1% in 2004 to 74.8% in 2014 (p = 0.002). Before PSM, there was a significant difference in breast cancer‐specific survival (BCSS) among the treatment arms. Patients who received RT had better BCSS, the 5‐year BCSS was 40.5%, 52.3%, 41.5%, and 47.7% in patients treated with BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively (p < 0.001). In the PSM cohort, patients treated with BCS alone had lower 5‐year BCSS compared to those treated with BCS+RT (43.9% and 52.1%, p = 0.002). However, there were comparable 5‐year BCSS between BCS+RT and MAST alone groups (51.3% and 50.1%, p = 0.872), and BCS+RT and MAST+RT cohorts (51.5% and 55.7%, p = 0.333). Similar results were confirmed in multivariate analysis.ConclusionsPostoperative RT improves BCSS in patients with de novo stage IV breast cancer, and BCS+RT shows a non‐inferior outcome compared to MAST+RT. BCS+RT may be the optimal local management of de novo stage IV breast cancer.

Comparison of survival in non-metastatic inflammatory and other T4 breast cancers: a SEER population-based analysis

BackgroundPrevious studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored.MethodsSurveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type.ResultsOut of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR−/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR−/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR−/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216–0.902; P = 0.025) and HR−/HER2- cohort (HR = 1.738; 95% CI: 1.192–2.534; P = 0.004).ConclusionsPatients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR−/HER2+ subtype is associated with a better outcome, and HR−/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.

Survival of Breast-Conserving Surgery Plus Radiotherapy versus Total Mastectomy in Early Breast Cancer.

Breast-conserving surgery (BCS) has been reported to have better survival rates when compared with total mastectomy (TM) in early breast cancer. We evaluated the long-term outcomes of Korean women with early breast cancer who underwent either BCS plus radiotherapy (RT) or TM. In this population-based study, we evaluated 45,770 patients from the Korean Breast Cancer Registry (KBCR) who were diagnosed with early breast cancer, and divided them into the BCS + RT and TM groups. To minimize bias caused by factors other than the surgical method, we used exact match pairing of prognostic factors. We compared the 10-year overall survival (OS) and breast cancer-specific survival (BCSS) before and after exact matching. As the KBCR is a multicenter, online-based registry program, we used the Asan Medical Center (AMC) database, a single-center database, to validate the results from the KBCR database. In both the KBCR and AMC cohorts, the BCS+RT group showed better OS and BCSS than the TM group, before and after exact matching. For the KBCR cohort after exact matching, the hazard ratios for OS and BCSS were 1.541 (95% confidence interval [CI] 1.392-1.707, p<0.001) and 1.405 (95% CI 1.183-1.668, p<0.001), respectively, favoring the BCS+RT group. For the AMC cohort after exact matching, the hazard ratios for OS and BCSS were 1.854 (95% CI 1.476-2.328, p<0.001) and 1.807 (95% CI 1.186-2.752, p=0.006), respectively. Our results suggest that BCS+RT is at least equivalent to TM in terms of OS and may affect treatment decisions in early breast cancer patients.

Staging for Breast Cancer With Internal Mammary Lymph Nodes Metastasis: Utility of Incorporating Biologic Factors.

PurposeTo validate the 8th edition of the American Joint Committee on Cancer (AJCC) pathological prognostic staging system for breast cancer patients with internal mammary lymph nodes (IMN) metastasis (N3b disease, stage IIIC in 7th AJCC anatomical staging).MethodsBreast cancer patients with IMN metastasis diagnosed between 2010 and 2014 were retrieved from the Surveillance, Epidemiology, and End Results program. Chi-squared test, Log-rank test, Kaplan-Meier method, and Cox proportional hazard analysis were applied to statistical analysis.ResultsWe included 678 patients with N3b disease in this study. Overall, 68.4% of patients were downstaged to IIIA and IIIB diseases from the 7th anatomical staging to 8th pathological prognostic staging. The new pathological prognostic staging system had better discriminatory value on prognosis prediction among IMN-metastasized breast cancer patients, with a 5-year breast cancer-specific survival (BCSS) of 92.7, 77.4, and 66.0% in stage IIIA, IIIB, and IIIC diseases, respectively (P<0.0001), and the 5-year overall survival (OS) rates was 85.9, 72.1, and 58.7%, respectively (P<0.0001). The results of the multivariate prognostic analysis showed that the new pathological prognostic staging was the independent prognosis related to BCSS and OS, the 8th AJCC pathological prognostic stages showed worse BCSS and OS with gradually increased hazard ratios.ConclusionThe 8th AJCC pathological prognostic staging system offers more refined prognostic stratification to IMN-metastasized breast cancer patients and endorses its use in routine clinical practice for this specific subgroup of breast cancer.

Survival Outcomes for Metaplastic Breast Cancer Differ by Histologic Subtype.

Metaplastic breast carcinoma (MBC) is a rare, aggressive subtype of breast cancer associated with poorer overall survival than other triple-negative breast cancers. This study sought to compare survival outcomes among histologic subtypes of MBC with those of non-metaplastic triple-negative breast cancer. Clinicopathologic and treatment data for all patients with non-metastatic, pure MBC undergoing surgery from 1995 to 2017 and for a large cohort of patients with other types of triple-negative breast cancer during that period were collected from an institutional database. The MBC tumors were classified as having squamous, spindle, heterologous mesenchymal, or mixed histology. Survival outcomes were compared using the Kaplan-Meier method. Of 132 MBC patients, those with heterologous mesenchymal MBC (n = 45) had the best 5-year overall and breast cancer-specific survival (BCSS, 88%; 95% confidence interval [CI], 0.78-0.99), whereas those with squamous MBC had the worst survival (BCSS, 56%; 95% CI, 0.32-0.79). Overall survival, BCSS, and recurrence-free survival were worse for the patients with MBC than for the patients who had non-MBC triple-negative breast cancer, with a clinicopathologically adjusted recurrence hazard ratio of 2.4 (95% CI, 1.6-3.3; p < 0.001). Of the 10 MBC patients who received neoadjuvant chemotherapy, 4 progressed while receiving treatment, and 3 had no response. Metaplastic breast carcinoma is associated with worse survival than other triple-negative breast cancers. The heterologous mesenchymal subtype is associated with the best survival, whereas the squamous subtype is associated with the worst survival. These data call for research to identify therapies tailored to MBC's unique biology.

Ten-year survival outcome of breast cancer patients in India.

INTRODUCTION:Breast cancer is the most frequently diagnosed cancer among women in India; however, there are no studies addressing long-term survival (10 years and above). This study sought to evaluate long-term oncological outcome among women with breast cancer treated with a curative intent.MATERIALS AND METHODS:This is a retrospective cohort analysis of 1301 breast cancer patients of all stages who had received primary treatment with curative intent from 2004 to 2010 at a single cancer institution of India.RESULTS:A total of 1301 breast cancer patients were available for final analysis. The median age was 51 years (range, 21–86 years). 70.25% of the patients had early breast cancer (EBC), 21.9% had locally advanced breast cancer, and 7.85% of the patients with de novo metastatic disease also underwent surgery. 56.5% of the patients had hormone-sensitive tumors, human epidermal growth factor receptor 2 over expression was seen in 17%, and triple-negative tumors accounted for 26.2% of the patients. The 5- and 10-year overall survival (OS) of the entire cohort was 79% and 66%, and the 5- and 10-year breast cancer-specific survival (BCSS) was 79% and 70%, respectively. OS and BCSS were 51% and 58%, respectively, at 15-year follow-up after primary cancer treatment. On multivariate analysis, the factors associated with prolonged survival were age ≤50 years, EBC, and treatment during the later period (2008–2010).CONCLUSION:Difference between OS and BCSS was found to have an increasing trend during 10–15-year follow-up, the difference being 4% at 10 years and 7% at 15 years. Age ≤50 years, early-stage disease at presentation, and primary cancer treatment in later years (2008–2010) were favorable predictors for 10-year survival.

Local Recurrence after Treatment of Ductal Carcinoma In Situ: A Comprehensive Overview.

Patients with DCIS have an excellent long-term prognosis with a 10-year breast cancer-specific survival around 98%. Treatment has the goal to prevent the development of an invasive breast cancer and to minimize the risk for a second breast cancer event, and published studies have shown a substantial decrease in invasive local recurrence rates over time. Approximately 50% of the local recurrences after BCS for a primary DCIS are invasive and 8.5% of them node-positive. Experiencing an ipsilateral invasive recurrence after a primary DCIS does significantly increase the risk of breast cancer death, while this is not seen after a DCIS recurrence. Radical surgery remains crucial to minimize the risk of local recurrence, and adjuvant radiotherapy reduces the risk of local recurrence by at least 50%. At recurrence, a repeat-BCS should be considered as it offers a good local control in properly selected patients and an overall and breast cancer-specific survival comparable to that seen after mastectomy.

The role of chemotherapy in patients with T1bN0M0 triple-negative breast cancer: a real-world competing risk analysis.

The objective of the present study was to implement Kaplan-Meier analysis, competing risk analysis, and propensity score matching to evaluate whether the patients with T1bN0M0 triple-negative breast (TNBC) could benefit from adjuvant chemotherapy. A total of 1849 patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. All eligible patients were divided into two cohorts, the chemotherapy (1155 patients) and the no-chemotherapy (694 patients) cohorts. Similar 5-year breast cancer-specific survival (BCSS) was observed in the chemotherapy and no-chemotherapy cohorts (96.1% vs. 96.0%, p=0.820). The results of the competing risk analysis showed a comparable 5-year breast cancer-specific death (BCSD) in both groups (chemotherapy 3.6% vs. no-chemotherapy 3.4%, p=0.778). Also, a higher 5-year other causes death (OCD) was observed in the no-chemotherapy cohort (0.7% vs. 5.4%, p<0.001). Multivariable competing risks regression models showed no association between chemotherapy and BCSS (HR, 1.21; 95%CI, 0.64-2.31; p=0.560). After 1:1 PSM, no significant difference was also observed for BCSD and OCD between two cohorts. The value of adjuvant chemotherapy in patients with T1bN0M0 TNBC is less than the present guidelines recommend, suggesting that de-escalated treatment could be a potentially beneficial strategy in appropriately selected patients.

The prognostic and predictive value of the 8th American Joint Committee on Cancer (AJCC) staging system among early breast cancer patients aged

This study respectively analyzed the prognostic value and the role in treatment decision-making [breast-conserving surgery (BCS) + radiotherapy (RT) or mastectomy (MAST)] of the 8th American Joint Committee on Cancer (AJCC) pathological prognostic staging system compared with the 7th AJCC anatomical staging system among early breast cancer patients aged <50 years. Patients with T1-2N0M0 breast cancer aged <50 years were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2014. Breast cancer-specific survival (BCSS) was used as the primary endpoint. Chi-squared test, receiver operating characteristics analysis, Kaplan-Meier method, and multivariate Cox proportional models were used to conduct statistical analysis. A total of 22,640 female patients were identified, and 24.4% of them reallocated to new stage groups from the 7th to the 8th AJCC staging. Among them, 46.2% (n=10,450) and 53.8% (n=12,190) of patients received BCS + RT and MAST, respectively. The 8th AJCC staging system was an independent prognostic factor for BCSS. Patients treated with BCS + RT had better BCSS compared to those treated with MAST (P<0.001). According to the 8th AJCC staging, BCS + RT could improve 5-year BCSS compared with MAST in patients with stage IA (P=0.006) and stage IB (P=0.001) diseases, while comparable BCSS was found between the two treatment arms in patients' stage IIA disease (P=0.366). Multivariate analyses replicated similar findings after stratification by the 8th AJCC stages. In patients with T1-2N0 breast cancer and aged <50 years, the 8th AJCC pathological staging system provides accurate prognostic information than the 7th anatomical staging. BCS + RT is the optimal local management for stage IA and IB diseases, while it is the optional management in stage IIA disease according to the 8th AJCC staging.

Prognostic and Predictive Value of the American Joint Committee on Cancer Pathological Prognostic Staging System in Nodal Micrometastatic Breast Cancer.

IntroductionTo investigate the prognostic and predictive effect of the American Joint Committee on Cancer (AJCC) 8th edition pathological prognostic staging system in patients with T1-2N1micM0 breast cancer who underwent mastectomy.MethodsData from T1-2N1micM0 breast cancer patients who underwent mastectomy from 2010–2014 were obtained from the Surveillance, Epidemiology, and End Results program. The chi-square test, binomial logistics regression, receiver-operating characteristics curve, competing-risk regression model, Cox proportional hazards regression model, and proportional hazard assumption were used for statistical analyses.ResultsWe identified 4,729 patients, including 1,062 patients were received postmastectomy radiotherapy (PMRT). Stage change occurred in 88.2% of the patients, of which 84.4% were downstaged and 3.7% were upstaged. Patients with higher pathological prognostic stages were independently predicted to receive PMRT. The 5-year breast cancer-specific survival (BCSS) was 97.5, 93.7, 90.1, 86.0, and 73.5% in disease stages IA, IB, IIA, IIB, and IIIA, respectively, according to the 8th edition criteria (P < 0.001). The AJCC 8th edition demonstrated moderate discriminative ability, and it had a significantly better ability to predict the BCSS than the AJCC 7th edition criteria (P < 0.001). The multivariate prognostic analysis showed that the new pathological prognostic staging was an independent prognostic factor affecting the BCSS. The BCSS worsened with an increase in the stage. The PMRT did not affect the BCSS regardless of the pathological prognostic stage. Similar trends were found using the competing-risks regression model.ConclusionsThe 8th AJCC breast cancer pathological prognostic staging system downstaged 84.4% of patients with T1-2N1micM0 disease and the survival outcome prediction with this staging system was more accurate than the AJCC 7th edition system. Our study does not support using the prognostic stage as a guideline to escalate of PMRT.

Survival Outcome and Impact of Chemotherapy in T1 Node-Negative Triple-Negative Breast Cancer: A SEER Database Analysis.

Objective Although triple-negative breast cancer (TNBC) has been considered to be an aggressive disease, the outcome of small-tumor (T1abcN0M0) TNBC and the effect of adjuvant chemotherapy on TNBC survival remain controversial. Methods We identified 4565 T1abcN0M0 TNBC patients in the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2015. After propensity score matching (PSM), 3214 patients were finally analyzed. Survival rates were compared among T1a, T1b, and T1c patients and between patients with and without adjuvant chemotherapy. Results We classified 424, 1040, and 3101 cases as T1a, T1b, and T1c TNBC, respectively. A total of 2760 (60.5%) patients received adjuvant chemotherapy, accounting for 25.5%, 56.0%, and 66.8% of T1a, T1b, and T1c patients, respectively. Rates of 5-year breast cancer-specific survival (BCSS) for T1a, T1b, and T1c patients receiving chemotherapy were 97.8%, 94.1%, and 94.5%, respectively, compared with 97.2%, 94.0%, and 89.9% in patients without chemotherapy. Patients receiving adjuvant chemotherapy had higher 5-year BCSS (94.5% vs. 89.9%, P = 0.004) in the T1c subgroup, but no significant difference was detected in T1a or T1b patients due to adjuvant chemotherapy. Conclusion Small-tumor TNBC showed very good prognosis. Adjuvant chemotherapy improved prognosis in T1c TNBC cases to a greater extent than in T1a and T1b patients. More large-scale clinical trials are needed, and further study should be conducted to determine appropriate adjuvant chemotherapy for T1c TNBC patients.

Adjuvant chemotherapy and survival in women aged 70 years and older with triple-negative breast cancer: a Swedish population-based propensity score-matched analysis

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer associated with poor survival, in which adjuvant systemic treatments are limited to chemotherapy. Due to competing mortality risks and comorbidities, older patients with TNBC are often undertreated with adjuvant chemotherapy, and clinical trials on this problem are scarce, despite a growing patient population. This study aimed to assess outcomes for patients aged 70 years and older with TNBC with or without chemotherapy in a national population-based registry, to provide information that can assist in treatment decisions for these patients. In this population-based registry study, data on all patients aged 70 years and older diagnosed with primary early TNBC (larger than 5 mm in diameter and without distant metastasis) and surgically treated between Jan 1, 2009, and Dec 31, 2016, were retrieved from the Swedish National Breast Cancer Register, the Swedish Patient Register, and the Swedish Cause of Death Register. Patients with incomplete data (on oestrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2 status, surgical procedure in the breast, or information about chemotherapy) were excluded. A propensity score-matched (PSM) model was used to examine the outcomes of adjuvant chemotherapy on 5-year breast cancer-specific survival (BCSS) and 5-year overall survival (OS), adjusted for age, tumour size, tumour grade, nodal status, and comorbidities. Of 1130 women eligible for analysis, 368 (32·6%) received adjuvant chemotherapy, 45 (4·0%) received neoadjuvant treatment, and 717 (63·5%) did not receive chemotherapy. 5-year BCSS was significantly improved in patients who received adjuvant chemotherapy (85% [95% CI 81-89]) compared with patients who did not receive chemotherapy (68% [64-72]; p<0·0001). A similar benefit was observed in 5-year OS (79% [95% CI 75-84] vs 49% [45-53]; p<0·0001). In our PSM analysis, 5-year BCSS in patients treated with adjuvant chemotherapy was 83% (95% CI 78-89), versus 73% (67-80; p=0·014) in patients not treated with chemotherapy. 5-year OS in patients treated with adjuvant chemotherapy was 75% (95% CI 69-82), versus 63% (57-71; p=0·029) in patients who did not receive chemotherapy. In this PSM registry analysis of surgically treated female patients aged 70 years and older with TNBC without distant metastasis, we identified a significant benefit both in 5-year BCSS and 5-year OS with adjuvant chemotherapy versus no chemotherapy, which persisted when adjusting for age and comorbidities. These results underline the importance of considering adjuvant chemotherapy in older patients. Knut and Alice Wallenberg Foundation, Assar Gabrielsson Foundation.

The effect of postmastectomy radiotherapy in node-positive triple-negative breast cancer

BackgroundThe value of postmastectomy radiotherapy (PMRT) for pathological node-positive triple-negative breast cancers (TNBC) remains debatable. The aim of this population-based retrospective study was to evaluate the effect of PMRT on survival outcomes in this population.MethodsPatients diagnosed with stage T1-4N1-N3M0 TNBC between 2010 and 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We used univariate and multivariate Cox regression hazards method to determine the independent prognostic factors associated with 3-year breast cancer-specific survival (BCSS). The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups.ResultsOf the 4398 patients included in this study, 2649 (60.2%) received PMRT. Younger age, black ethnicity, and advanced tumor (T) and nodal (N) stage were the independent predictors associated with PMRT receipt (all P < 0.05). Patients who received PMRT showed better 3-year BCSS (OR = 0.720, 95% CI = 0.642–0.808, P < 0.001) than those that did not. The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. The results showed that PMRT was associated with better 3-year BCSS in patients with stage T3–4N1 (P = 0.042), T1-4N2 (P < 0.001), and T1-4N3 (P < 0.001), while comparable 3-year BCSS was found between the PMRT and non-PMRT cohorts with T1–2N1 disease (P = 0.191).ConclusionsRadiotherapy achieved better 3-year BCSS in TNBC patients with stage T3–4N1 and T1-4N2–3 disease. However, no survival benefit was found with the addition of PMRT in patients with T1–2N1 TNBC.

Aggressive Local Treatment Improves Survival in Stage IV Breast Cancer With Synchronous Metastasis.

IntroductionTo investigate the effect of local treatment strategy on survival outcome in de novo stage IV breast cancer patients who received chemotherapy.MethodsWe identified stage IV breast cancers that presented with synchronous metastasis from the Surveillance, Epidemiology, and End Results database. Binomial logistic regression, Kaplan–Meier survival curves, propensity score matching (PSM), and multivariate Cox regression model were used for statistical analyses.ResultsWe identified 5,374 patients in total, including 2,319 (43.2%), 2,137 (39.8%), and 918 (17.1%) patients who received surgery alone, surgery+radiotherapy, and radiotherapy alone, respectively. The probability of patients receiving surgery alone decreased over time, and the probability of patients receiving radiotherapy alone increased over time. However, no significant difference was observed in the probability of patients receiving postoperative radiotherapy (P = 0.291). The 3-year breast cancer-specific survival (BCSS) in patients treated with surgery alone, radiotherapy alone, and surgery+radiotherapy was 57.1, 35.9, and 63.9%, respectively (P < 0.001). The local treatment strategy was the independent prognostic factor related to BCSS. Using surgery alone as the reference, radiotherapy alone was related to lower BCSS (P < 0.001), while additional radiotherapy after surgery improved BCSS (P < 0.001). Similar results were observed using PSM.ConclusionsCompared to radiotherapy alone, surgery to the primary site may confer a survival benefit in stage IV breast cancer with synchronous metastasis, and additional postoperative radiotherapy further improves outcome after primary tumor removal. Local treatment can only be an option in highly selected patients with de novo stage IV disease in the treatment guidelines. More prospective studies are needed to investigate the role of local management for this patient subset.

Effect of node status on breast cancer survival by subtype: a single-center retrospective cohort study.

BackgroundNodal involvement and molecular subtypes were used as independent prognostic indicators in women with breast cancer. However, they did not adequately address the effect of node status by subtype in outcomes.MethodsWe performed a retrospective review of data from 2004 to 2011 from the Affiliated Union Hospital of Fujian Medical University with newly diagnosed stage I to III breast cancer to investigate the relationship between node status and 5-year disease-free survival (DFS) and breast cancer-specific survival (BCSS) by molecular subtype. The Cox proportional hazards model was used for multivariate analysis.ResultsMedian follow-up time was 6.4 years. Luminal HER2 and luminal B were the subtypes with a higher percentage of nodal involvement and high-volume nodal involvement (≥4 positive lymph node) than luminal A. The effect of node status on the prognosis varied with molecular subtype. There was no difference in 5-year DFS and BCSS between stage N1 or N2 and N0 groups in patients with luminal A disease. Nodal involvement in women with the luminal B, luminal HER2, and triple-negative subtypes showed significant difference for 5-year DFS and BCSS compared to the node negative group.ConclusionsNodal involvement seems to be associated with worse survival in women with the luminal B, luminal HER2, and triple-negative subtypes, but not with the luminal A subtype.

Predicting Survival Benefit of Sparing Sentinel Lymph Node Biopsy in Low-Risk Elderly Patients With Early Breast Cancer: A Population-Based Analysis.

Objective: The application of sentinel lymph node biopsy (SLNB) in elderly patients with early breast cancer remains somewhat controversial. This study aimed to establish individualized nomograms to predict survival outcomes of elderly patients with and without SLNB and find out which patients could avoid SLNB.Methods: A total of 39,962 ≥70-year-old patients diagnosed with T1–T2 breast cancer in 2010–2015 were included from the Surveillance, Epidemiology, and End Results (SEER) program and were divided into the training set (n = 29,971) and the validation set (n = 9,991). Axillary surgery was not specified in the SEER database, and we defined removing one to five lymph nodes as SLNB. Survival analysis was performed using the Kaplan–Meier plot and log-rank test. Multivariate Cox analysis was utilized to identify risk factors for overall survival (OS) and breast-cancer-specific survival (BCSS). Nomograms and a risk stratification model were constructed.Results: In the training set, patients with SLNB had better OS (adjusted HR 0.57, P < 0.001) and BCSS (adjusted HR 0.55, P < 0.001) than patients without SLNB. Multivariate COX analysis identified age, marital status, grade, subtype, T stage, and radiation as independent risk factors for OS and BCSS in both SLNB and non-SLNB groups (all P < 0.05). They were subsequently incorporated to establish nomograms to predict 3- and 5-year OS and BCSS for patients with or without SLNB. The concordance index ranged from 0.687 to 0.820, and calibration curves in the internal set and external set all demonstrated sufficient accuracies and good predictive capabilities. Further, we generated a risk stratification model which indicated that SLNB improved OS and BCSS in high-risk group (OS: HR 0.49, P < 0.001; BCSS: HR 0.54, P < 0.001), but not in the low-risk group (all P > 0.05).Conclusion: Well-validated nomograms and a risk stratification model were constructed to evaluate survival benefit from SLNB in elderly patients with early-stage breast cancer. SLNB was important for patients in the high-risk group but could be omitted in the low-risk group without sacrificing survival. This study could assist clinicians and elderly patients to weigh the risk–benefit of SLNB and make individualized decisions. We look forward to more powerful evidence from prospective trials.

Incorporation of biologic factors for the staging of de novo stage IV breast cancer

This study aimed to investigate the prognostic value of biological factors, including histological grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status in de novo stage IV breast cancer. Based on eligibility, patient data deposited between 2010 and 2014 were collected from the surveillance, epidemiology, and end results database. The receiver operating characteristics curve, Kaplan–Meier analysis, and Cox proportional hazard analysis were used for analysis. We included 8725 patients with a median 3-year breast cancer-specific survival (BCSS) of 52.6%. Higher histologic grade, HER2-negative, ER-negative, and PR-negative disease were significantly associated with lower BCSS in the multivariate prognostic analysis. A risk score staging system separated patients into four risk groups. The risk score was assigned according to a point system: 1 point for grade 3, 1 point if hormone receptor-negative, and 1 point if HER2-negative. The 3-year BCSS was 76.3%, 64.5%, 48.5%, and 23.7% in patients with 0, 1, 2, and 3 points, respectively, with a median BCSS of 72, 52, 35, and 16 months, respectively (P < 0.001). The multivariate prognostic analysis showed that the risk score staging system was an independent prognostic factor associated with BCSS. Patients with a higher risk score had a lower BCSS. Sensitivity analyses replicated similar findings after stratification according to tumor stage, nodal stage, the sites of distant metastasis, and the number of distant metastasis. In conclusion, our risk score staging system shows promise for the prognostic stratification of de novo stage IV breast cancer.

Association between breast cancer risk and disease aggressiveness: Characterizing underlying gene expression patterns.

The association between breast cancer risk defined by the Tyrer‐Cuzick score (TC) and disease prognosis is not well established. Here, we investigated the relationship between 5‐year TC and disease aggressiveness and then characterized underlying molecular processes. In a case‐only study (n = 2474), we studied the association of TC with molecular subtypes and tumor characteristics. In a subset of patients (n = 672), we correlated gene expression to TC and computed a low‐risk TC gene expression (TC‐Gx) profile, that is, a profile expected to be negatively associated with risk, which we used to test for association with disease aggressiveness. We performed enrichment analysis to pinpoint molecular processes likely to be altered in low‐risk tumors. A higher TC was found to be inversely associated with more aggressive surrogate molecular subtypes and tumor characteristics (P < .05) including Ki‐67 proliferation status (P < 5 × 10−07). Our low‐risk TC‐Gx, based on the weighted sum of 37 expression values of genes strongly correlated with TC, was associated with basal‐like (P < 5 × 10−13), HER2‐enriched subtype (P < 5 × 10−07) and worse 10‐year breast cancer‐specific survival (log‐rank P < 5 × 10−04). Associations between low‐risk TC‐Gx and more aggressive molecular subtypes were replicated in an independent cohort from The Cancer Genome Atlas database (n = 975). Gene expression that correlated with low TC was enriched in proliferation and oncogenic signaling pathways (FDR < 0.05). Moreover, higher proliferation was a key factor explaining the association with worse survival. Women who developed breast cancer despite having a low risk were diagnosed with more aggressive tumors and had a worse prognosis, most likely driven by increased proliferation. Our findings imply the need to establish risk factors associated with more aggressive breast cancer subtypes.