The association between body fatness and mortality among breast cancer survivors: results from a prospective cohort study.

Evidence linking body fatness to breast cancer (BC) prognosis is limited. While it seems that excess adiposity is associated with poorer BC survival, there is uncertainty over whether weight changes reduce mortality. This study aimed to assess the association between body fatness and weight changes pre- and postdiagnosis and overall mortality and BC-specific mortality among BC survivors. Our study included 13,624 BC survivors from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, with a mean follow-up of 8.6 years after diagnosis. Anthropometric data were obtained at recruitment for all cases and at a second assessment during follow-up for a subsample. We measured general obesity using the body mass index (BMI), whereas waist circumference and A Body Shape Index were used as measures of abdominal obesity. The annual weight change was calculated for cases with two weight assessments. The association with overall mortality and BC-specific mortality were based on a multivariable Cox and Fine and Gray models, respectively. We performed Mendelian randomization (MR) analysis to investigate the potential causal association. Five-unit higher BMI prediagnosis was associated with a 10% (95% confidence interval: 5-15%) increase in overall mortality and 7% (0-15%) increase in dying from BC. Women with abdominal obesity demonstrated a 23% (11-37%) increase in overall mortality, independent of the association of BMI. Results related to weight change postdiagnosis suggested a U-shaped relationship with BC-specific mortality, with higher risk associated with losing weight or gaining > 2% of the weight annually. MR analyses were consistent with the identified associations. Our results support the detrimental association of excess body fatness on the survival of women with BC. Substantial weight changes postdiagnosis may be associated with poorer survival.

Consumption of sugar-sweetened and artificially sweetened beverages and breast cancer survival.

BACKGROUND: The activation of insulin pathways is hypothesized to promote tumor growth and worsen breast cancer survival. Sugar-sweetened beverages (SSBs) can lead to a higher risk of insulin resistance and may affect survival. The authors prospectively evaluated the relation of postdiagnostic SSB and artificially sweetened beverage (ASB) consumption with mortality among women with breast cancer. METHODS: In total, 8863 women with stage I through III breast cancer were identified during follow-up of the Nurses' Health Study (NHS; 1980-2010) and Nurses' Health Study II (NHSII; 1991-2011). Women completed a validated food frequency questionnaire every 4 years after diagnosis and were followed until death or the end of follow-up (2014 for the NHS and 2015 for the NHSII). Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-specific and all-cause mortality after adjusting for measures of adiposity and other potential predictors of cancer survival. RESULTS: With a median follow-up of 11.5 years, 2482 deaths were prospectively documented, including 1050 deaths from breast cancer. Compared with women who had no consumption, women who had SSB consumption after diagnosis had higher breast cancer-specific mortality (>1 to 3 servings per week: HR, 1.31 [95% CI, 1.09-1.58]; >3 servings per week: HR, 1.35 [95% CI, 1.12-1.62]; Ptrend = .001) and all-cause mortality (>1 to 3 servings per week: HR, 1.21 [95% CI, 1.07-1.37]; >3 servings per week: HR, 1.28 [95% CI, 1.13-1.45]; Ptrend = .0001). In contrast, ASB consumption was not associated with higher breast cancer-specific or all-cause mortality. Furthermore, replacing 1 serving per day of SSB consumption with 1 serving per day of ASB consumption was not associated with a lower risk of mortality. CONCLUSIONS: Higher postdiagnostic SSB consumption among breast cancer survivors was associated with higher breast cancer-specific mortality and death from all causes.

Breast Cancer-Specific Mortality in Small-Sized Tumor with Stage IV Breast Cancer: A Population-Based Study.

BACKGROUND: Small-sized primary tumor does not always indicate a better prognosis. We hypothesized that very small primary breast tumors with extensive lymph node (LN) metastases represented an aggressive biologic behavior in stage IV disease. MATERIALS AND METHODS: Data between 2010 and 2015 were retrieved retrospectively from the Surveillance, Epidemiology, and End Results database with inclusion criteria of female sex, unilateral, metastatic, and T1/2 invasive ductal carcinoma. Primary study variables included T stage, N stage, grade, metastatic sites, number of involved sites, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status. Kaplan-Meier and adjusted Cox proportional hazards models with interaction terms were used. One-, 2- and 3-year breast cancer-specific mortality (BCSM) was examined according to tumor size. RESULTS: We identified 5,340 eligible patients with breast cancer. In multivariate analysis, race, age, grade, molecular subtype, surgery, brain metastases, and liver metastases were found to be independently associated with BCSM. For T1 tumors, the N0, N1, and N2+ groups had the same BCSM. In tumors smaller than 50 mm, the 1-, 2-, and 3-year BCSM did not decline with the decrease of tumor size. For triple-negative breast cancers (TNBCs), the T1a/T1bN2+ group had significantly worse BCSM than any other group did. CONCLUSION: Patients with stage IV cancer with small-sized tumors may have BCSM as high as those with larger tumors. In TNBCs, very small tumors with severe LN involvement are associated with the worst BCSM. Continued efforts are needed to further investigate Ta1/T1bN2 + M1 TNBCs and individualize the treatment for affected patients. IMPLICATIONS FOR PRACTICE: This study revealed that for stage IV breast cancer, smaller primary tumors were not always associated with better breast cancer-specific mortality. This study illustrated that very small triple-negative breast cancers (TNBCs) with extensive regional lymph node involvement may be a surrogate for biologically aggressive disease. Because of poor prognosis of T1a/T1bN2+ TNBCs, there might be an urgent need of more individualized treatment for affected patients. Future correlative studies ought to focus on the genetic and molecular differences in Ta1/T1bN2+ TNBCs that contribute to the biological behavior. Clarification of the regulation mechanism of very small-sized primary TNBCs with metastatic outgrowth in nodes and distant sites will play an integral role in developing targeted therapies.

Increased risk of breast cancer-specific mortality among cancer survivors who developed breast cancer as a second malignancy.

BACKGROUND: Cancer survivors who develop breast cancer as a second malignancy (BCa-2) are common. Yet, little is known about the prognosis of BCa-2 compared to first primary breast cancer (BCa-1). METHODS: Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study including 883,881 patients with BCa-1 and 36,313 patients with BCa-2 during 1990-2015. Compared with patients with BCa-1, we calculated hazard ratios (HRs) of breast cancer-specific mortality among patients with BCa-2, using multivariable Cox regression. RESULTS: During the follow-up (median 5.5 years), 114,964 and 3829 breast cancer-specific deaths were identified among BCa-1 and BCa-2 patients, respectively. Patients with BCa-2 had more favorable tumor characteristics and received less intensive treatment e.g., surgery and chemo-/radio-therapy, compared to patients with BCa-1. When adjusting for demographic factors, patients with BCa-2 were at similar risk of breast cancer-specific mortality (HR 1.00, 95% CI 0.97-1.03) compared to patients with BCa-1. However, when additionally controlling for tumor characteristics and treatment modes, BCa-2 patients were at an increased risk of breast cancer-specific mortality (HR 1.11, 95% CI 1.08-1.15). The risk elevation was particularly greater when the first malignancy was lung, bladder, ovarian or blood malignancy (HRs 1.16-1.85), or when the first malignancy was treated with chemotherapy and radiotherapy (HR 1.44, 95% CI 1.28-1.63). CONCLUSIONS: Overall, patients with BCa-2 have worse breast cancer-specific survival, compared with their BCa-1 counterparts, although the risk elevation is mild. High-risk subgroups based on first malignancy's characteristics may be considered for active clinical management.

The association of delay in curative intent treatment with survival among breast cancer patients: findings from the Women's Health Initiative.

PURPOSE: Delays in adjuvant breast cancer (BC) therapy have been shown to worsen outcomes. However, thus far studies have only evaluated delays to initial treatment, or a particular modality, such as chemotherapy, leaving uncertainty about the role of delay to subsequent therapy and the effects of cumulative delay, on outcomes. We investigated the associations of delays across treatment modalities with survival. METHODS: We included 3368 women with incident stage I-III BC in the Women's Health Initiative (WHI) enrolled in fee-for-service Medicare who underwent definitive surgery. This prospective analysis characterized treatment delays by linking WHI study records to Medicare claims. Delays were defined as > 8 weeks to surgery, chemotherapy, and radiation from diagnosis or prior treatment. We used Cox proportional hazards models to estimate BC-specific mortality (BCSM) and all-cause mortality (ACM) in relation to treatment delays. RESULTS: We found 21.8% of women experienced delay to at least one therapy modality. In adjusted analysis, delay to chemotherapy was associated with a higher risk of BCSM (HR = 1.71; 95% CI 1.07-2.75) and ACM (HR = 1.39; 95% CI 1.02-1.90); delay in radiation increased BCSM risk (HR = 1.49; 95% CI 1.00-2.21) but not ACM risk (HR = 1.19; 95% CI 0.99-1.42). Delays across multiple treatment modalities increased BCSM risk threefold (95% CI 1.51-6.12) and ACM risk 2.3-fold (95% CI 1.50-3.50). CONCLUSIONS: A delay to a single treatment modality and delay to a greater extent an accumulation of delays were associated with higher BCSM and ACM after BC. Timely care throughout the continuum of breast cancer treatment is important for optimal outcomes.

Genetic variation in TNFα, PPARγ, and IRS-1 genes, and their association with breast-cancer survival in the HEAL cohort.

PURPOSE: Tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptor-γ (PPARγ), and insulin receptor substrate-1 (IRS-1) are associated with obesity, insulin resistance, and inflammation. Few data exist on associations between polymorphisms in these genes and mortality in breast cancer survivors. METHODS: We investigated associations between TNF-α -308G > A (rs1800629); PPARγ Pro12Ala (rs1801282); and IRS-1 Gly972Arg (rs1801278) polymorphisms and anthropometric variables, circulating levels of previously measured biomarkers, and tumor characteristics in 553 women enrolled in the Health, Eating, Activity, and Lifestyle Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer between 1995 and 1999 (median follow-up 14.7 years).  Using Cox proportional hazards models adjusted for possible confounders, we evaluated associations between these polymorphisms and mortality. RESULTS: Carriers of the PPARγ variant allele had statistically significantly lower rates of type 2 diabetes (P = 0.04), lower BMI (P = 0.01), and HOMA scores [P = 0.004; non-Hispanic White (NHWs) only]; carriers of the TNF-α variant A allele had higher serum glucose (P = 0.004, NHW only); and the IRS-1 variant was associated with higher leptin levels (P = 0.003, Hispanics only). There were no associations between any of the polymorphisms and tumor characteristics. Among 141 deaths, 62 were due to breast cancer. Carriers of the TNF-α-variant A allele had a decreased risk of breast-cancer-specific mortality [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.10-0.83] and all-cause mortality (HR 0.51; 95% CI 0.28-0.91). CONCLUSIONS: Neither the PPARγ nor the IRS-1 polymorphism was associated with mortality outcome. The TNF-α -308 G > A polymorphism was associated with reduced breast-cancer-specific and all-cause mortality.

Healthy lifestyle impact on breast cancer-specific and all-cause mortality.

PURPOSE: While several studies have evaluated the association of combined lifestyle factors on breast cancer-specific mortality, few have included Hispanic women. We constructed a "healthy behavior index" (HBI) and evaluated its associations with mortality in non-Hispanic White (NHW) and Hispanic women diagnosed with breast cancer from the southwestern U.S. METHODS: Diet and lifestyle questionnaires were analyzed for 837 women diagnosed with invasive breast cancer (1999-2004) in New Mexico as part of the 4-Corners Women's Health Study. An HBI score ranging from 0 to 12 was based on dietary pattern, physical activity, smoking, alcohol consumption, and body size and shape, with increasing scores representing less healthy characteristics. Hazard ratios for mortality over 14 years of follow-up were estimated for HBI quartiles using Cox proportional hazards models adjusting for education and stratified by ethnicity and stage at diagnosis. RESULTS: A significant increasing trend was observed across HBI quartiles among all women, NHW women, and those diagnosed with localized or regional/distant stage of disease for all-cause (AC) mortality (p-trend = 0.006, 0.002, 0.03, respectively). AC mortality was increased >2-fold for all women and NHW women in HBI Q4 versus Q1 (HR = 2.18, 2.65, respectively). The association was stronger in women with regional/distant than localized stage of disease (HR = 2.62, 1.94, respectively). Associations for Hispanics or breast cancer-specific mortality were not significant. CONCLUSIONS: These findings indicate the associations between the HBI and AC mortality, which appear to differ by ethnicity and stage at diagnosis. Interventions for breast cancer survivors should address the combination of lifestyle factors on prognosis.

Has racial difference in cause-specific death improved in older patients with late-stage breast cancer?

BACKGROUND: Research on temporal mortality trends for stage IV breast cancer is limited, especially among older patients by race. We evaluated factors associated with overall, breast cancer-specific and other-cause mortalities using contemporary population data. PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare linked data, we identified older women (≥ 66 years) with stage IV breast cancer diagnosed in 2002-2009. Overall mortality was estimated by the Kaplan-Meier method, compared by log-rank tests, and modeled by Cox models. Competing risk analysis was used to evaluate breast cancer-specific and other-cause mortalities. RESULTS: The median overall survival time for non-Hispanic blacks improved from 8.6 months in 2002-2003 to 9.9 months in 2007-2009, whereas that for non-Hispanic whites improved from 12.1 to 14.8 months. In the multivariate model, the risk of breast cancer-specific death for patients diagnosed in 2007-2009 was significantly lower (P = 0.02), whereas the risk of other-cause mortality changed little (P = 0.88) compared with those risks for patients diagnosed in 2002-2003. Non-Hispanic blacks had the higher risk of both mortality types compared with non-Hispanic whites; a diagnosis time-race interaction term was not statistically significant for either cause of death. CONCLUSION: Breast cancer-specific mortality among older women modestly improved from 2002 to 2009 across all races, but not other-cause mortality. Racial disparity in mortality persisted, but did not widen in this period. Efforts should be devoted to improving other-cause mortality for all women, with special attention toward decreasing breast cancer mortality for non-Hispanic black women.

Surgical Delay-Associated Mortality Risk Varies by Subtype in Loco-Regional Breast Cancer Patients in SEER-Medicare.

Substantial evidence supports that delay of surgery after breast cancer diagnosis is associated with increased mortality risk, leading to the introduction of a new Commission on Cancer quality measure for receipt of surgery within 60 days of diagnosis for non-neoadjuvant patients. Breast cancer subtype is a critical prognostic factor and determines treatment options; however, it remains unknown whether surgical delay-associated breast cancer-specific mortality (BCSM) risk differs by subtype. This retrospective cohort study aimed to assess whether the impact of delayed surgery on survival varies by subtype (hormone [HR]+/HER2-, HR-/HER2-, and HER2+) in patients with loco-regional breast cancer who received surgery as their first treatment between 2010-2017 using the SEER-Medicare. Continuous time to surgery from diagnostic biopsy (TTS; days) in reference to TTS = 30 days. BCSM were evaluated as flexibly dependent on continuous time (days) to surgery from diagnosis (TTS) using Cox proportional hazards and Fine and Gray competing-risk regression models, respectively, by HR status. Inverse propensity score-weighting was used to adjust for demographic, clinical, and treatment variables impacting TTS. Adjusted BCSM risk grew with increasing TTS across all subtypes, however, the pattern and extent of the association varied. HR+/HER2- patients exhibited the most pronounced increase in BCSM risk associated with TTS, with approximately exponential growth after 42 days, with adjusted subdistribution hazard ratios (sHR) of 1.21 (95% CI: 1.06-1.37) at TTS = 60 days, 1.79 (95% CI: 1.40-2.29) at TTS = 90 days, and 2.83 (95% CI: 1.76-4.55) at TTS = 120 days. In contrast, both HER2 + and HR-/HER2- patients showed slower, approximately linear growth in sHR, although non-significant in HR-HER2-.

Increased breast cancer mortality due to treatment delay and needle biopsy type: a retrospective analysis of SEER-medicare.

BACKGROUND: Substantial evidence indicates that delay of first treatment after diagnosis is associated with poorer survival outcomes in breast cancer. Accordingly, the Commission on Cancer introduced a quality measure for receipt of therapeutic surgery within 60 days of diagnostic biopsy for stage I-III breast cancer patients in the non-neoadjuvant setting. It is unknown, however, what may contribute to mortality associated with treatment delay. Therefore, we investigated whether biopsy type moderates the effect of the mortality risk posed by treatment delay. METHODS: Retrospective analysis of 31,306 women with stage I-III breast cancer diagnosed between 2003 and 2013 selected from the SEER-Medicare database was performed to determine whether needle biopsy type [core needle biopsy (CNB) or vacuum-assisted biopsy (VAB)] impacts time to treatment (TTT)-associated survival outcomes. Multivariable Fine-Gray competing risk survival models, adjusted for inverse propensity score weights, were used to determine the association between biopsy type, TTT, and breast cancer-specific mortality (BCSM). RESULTS: TTT ≥ 60 days was associated with 45% higher risk of BCSM (sHR = 1.45, 95% CI 1.24-1.69) compared to those with TTT < 60 days in stage I-III cases. Independent of TTT, CNB was associated with 28% higher risk of BCSM compared to VAB in stage II-III cases (sHR = 1.28, 95% CI 1.11-1.36), translating to a 2.7% and 4.0% absolute difference in BCSM at 5 and 10 years, respectively. However, in stage I cases, the BCSM risk was not associated with type of biopsy. CONCLUSIONS: Our results suggest that treatment delay ≥ 60 days is independently associated with poorer survival outcomes in breast cancer patients. In stage II-III, CNB is associated with higher BCSM than VAB. However, type of biopsy does not underlie TTT-associated breast cancer mortality risk.

Effect of post-diagnosis exercise on depression symptoms, physical functioning and mortality in breast cancer survivors: A systematic review and meta-analysis of randomized control trials.

BACKGROUND: Cancer is the second leading cause of death worldwide. Breast cancer, the most common cancer found in women, affects 2.1 million women annually and has the highest number of cancer related deaths. The objective of the current meta-analysis is to evaluate the effects of post-diagnosis exercises on depression, physical functioning, and mortality in breast cancer survivors. METHODS: The search for eligible articles was conducted through CINAHL, Medline/PubMed, Scopus, Cochrane, Emerald Insight and Web of Science, Embase database, MEDLINE In-Process, Elsevier, Google Scholar, PsycInfo, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Allied and Complementary Medicine (AMED), Biosis Previews, SPORTDiscus, PEDro scientific databases from 1974 to 2020. Following the exclusion procedure, 26 articles yielded for final analysis. The combined statistics for depression, physical functioning, and mortality in breast cancer survivors were calculated using standardized mean differences (SMD). Standard errors and 95% confidence intervals (CI) were converted to standard deviations as required. For mortality, combined statistics were calculated using hazard ratios (HR). The 95% CIs were converted to standard errors as required. The forest plots display point estimates and 95% CIs. RESULTS: Statistically significant improvements on levels of depression were identified following the exercise intervention, suggesting that post-diagnosis physical activity leads to a decrease in depression scores. Overall, post-diagnosis exercise led to a 37% reduction in the rate of breast cancer-specific mortality. The all-cause mortality rate was decreased by 39% with the inclusion of moderate physical activity as the part of daily routine. CONCLUSIONS: Future studies should look at how to improve the quality of life while incorporating physical activity as a daily routine after breast-cancer treatment.

Associations Between Circulating Insulin-Like Growth Factor 1 and Mortality in Women With Invasive Breast Cancer.

Background: Studies on the association between circulating insulin-like growth factor 1 (IGF1) and prognosis of breast cancer are limited. Whether this association is modified by insulin levels and clinical characteristics is unclear. Methods: Serum concentrations of IGF1 as well as IGF binding protein 3 (IGFBP3), IGF1/IGFBP3 ratio, insulin, and C-peptide were prospectively examined in 2,682 invasive breast cancer patients who received surgery in Ruijin Hospital, Shanghai, between 2012 and 2017. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence associated with different levels of IGF1 and other biomarkers with multivariable adjustment. Results: Compared with patients with low IGF1, patients with high IGF1 had a significantly lower risk of all-cause mortality (HR, 0.53; 95% CI, 0.29-0.96) and a borderline lower risk of breast cancer-specific mortality (HR, 0.53; 95% CI, 0.27-1.02). The inverse association between IGF1 and all-cause mortality was consistent across stratification subgroups but was more pronounced among patients with high insulin (HR, 0.40; 95% CI, 0.18-0.89), were premenopausal (HR, 0.34; 95% CI, 0.12-0.97), with a tumor size >2 cm (HR, 0.35; 95% CI, 0.17-0.73), with positive lymph node (HR, 0.49; 95% CI, 0.25-0.98), and with a high Ki-67 level (HR, 0.49; 95% CI, 0.26-0.95) (all P for interaction >0.05). No significant associations were found for IGFBP3, IGF1/IGFBP3 ratio, insulin, and C-peptide levels with all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence. Conclusion: Circulating IGF1 was inversely and independently associated with all-cause mortality in invasive breast cancer patients, and this association was consistent across clinical risk factors.

Predictors of 5-year local, regional, and distant recurrent events in a population-based cohort of breast cancer patients.

BACKGROUND: The study purpose was to identify tumor and surgeon predictors of local recurrence (LR), regional recurrence (RR), and distant metastasis (DM) after breast cancer (BC) surgery in a population-based cohort. METHODS: Consecutive BC surgical cases from 12 hospitals in South Central Ontario between May 2006 and October 2006 were included. Data collected on chart review included patient and tumor factors, surgery type, adjuvant treatment, surgeon specialty, surgeon case volume, and practice type. Univariate and multivariable survival analyses were performed. RESULTS: Median follow-up was 5.5 years for 402 patients (97% of sample). LR, RR, and DM occurred in 18 (4.5%), 10 (2.5%), and 47 (12%) patients, respectively. Significant predictors of BC recurrence (LR or RR or DM) were tumor size and grade, nodal status, and lymphovascular invasion on multivariable analysis. CONCLUSION: Tumor factors such as size, grade, lymphovascular invasion, and nodal status predicted BC recurrence, while practice type, surgeon specialty, and case volume did not.

Smoking increases risks of all-cause and breast cancer specific mortality in breast cancer individuals: a dose-response meta-analysis of prospective cohort studies involving 39725 breast cancer cases.

Smoking is associated with the risks of mortality from breast cancer (BC) or all causes in BC survivors. Two-stage dose-response meta-analysis was conducted. A search of PubMed and Embase was performed, and a random-effect model was used to yield summary hazard ratios (HRs). Eleven prospective cohort studies were included. The summary HR per 10 cigarettes/day, 10 pack-years, 10 years increase were 1.10 (95% confidence interval (CI) = 1.04-1.16), 1.09 (95% CI = 1.06-1.12), 1.10 (95% CI = 1.06-1.14) for BC specific mortality, and 1.15 (95% CI = 1.10-1.19), 1.15 (95% CI = 1.10-1.20), 1.17 (95% CI = 1.11-1.23) for all-cause mortality, respectively. The linear or non-linear associations between smoking and risks of mortality from BC or all causes were revealed. Subgroup analyses suggested a positive association between ever or former smoking and the risk of all-cause mortality in BC patients, especially in high doses consumption. In conclusion, higher smoking intensity, more cumulative amount of cigarettes consumption and longer time for smoking is associated with elevated risk of mortality from BC and all causes in BC individuals. The results regarding smoking cessation and "ever or former" smokers should be treated with caution due to limited studies.

Effect of tumor size on breast cancer-specific survival stratified by joint hormone receptor status in a SEER population-based study.

BACKGROUND & AIMS: The prognostic value of tumor size is variable. We aimed to characterize the interaction between tumor size and hormone receptor (HoR) status to determine breast cancer-specific mortality (BCSM). METHODS: We used the Surveillance, Epidemiology and End Results (SEER) registry to identify 328, 870 female patients diagnosed with invasive breast cancer from 1990 through 2010. Primary study variables included tumor size, joint HoR status and their corresponding relationship. Kaplan-Meier and adjusted Cox proportional hazards models with interaction terms were utilized. RESULTS: The multivariable analysis revealed a significant interaction between tumor size and HoR status (P < 0.001). Using tumors 61-70 mm in size as the reference for estrogen receptor-negative (ER-) and progesterone receptor-negative (PR-) disease, the hazard ratio (HR) for BCSM increased with increasing tumor size across nearly all categories. In the ER-positive (ER+) and PR-positive (PR+) group, however, patients with tumors > 50 mm had nearly identical BCSM rates (P = 0.127, P = 0.099 and P = 0.370 for 51-60 mm, 71-80 mm and > 80 mm tumors, respectively), whereas BCSM was positively correlated with tumors < 51 mm. CONCLUSIONS: The observation of identical HRs for BCSM among patients with ER+ and PR+ tumors >50 mm underscores the importance of individualized treatment. Our findings may contribute to a better understanding of breast cancer biology.