Breast Cancer-specific Death Research Articles

Abstract P2-13-03: Statin use and breast cancer survival – a Swedish nationwide study

Abstract Background: A sizeable body of evidence shows that statins can cease proliferation of breast cancer and prevent breast cancer recurrence. Given the epidemiological findings from other Scandinavian populations, we hypothesized that statins may have anticancer effects and therefore reduce cancer-related mortality in a Swedish population. This study investigates the association between both pre- and post diagnostic statin use and breast cancer outcome. Methods: A Swedish nation-wide retrospective cohort study of 20,559 Swedish women diagnosed with breast cancer (July 1st, 2005 through 2008). Dispensed statin medication was identified through the Swedish Prescription Registry. Breast cancer-specific death information was obtained from the national cause-of-death registry until December 31st, 2012. Cox regression models yielded hazard ratios (HR) and 95% confidence intervals (CI) regarding associations between statin use and breast cancer-specific and overall mortality. Results: During follow-up, a total of 4,678 patients died, whereof 2,669 were considered breast cancer-specific deaths. Compared to non- or irregular use, regular pre-diagnostic statin use was associated with lower risk of breast cancer-specific death (HR=0.77 (95%CI 0.63-0.95), P=0.014). When evaluating diabetes patients only (N=545), this association was strengthened (HR=0.63 (95%CI 0.40-0.98), P=0.044). Post diagnostic statin use was in similarity associated with lower risk of breast cancer–related death compared to non-use (HR=0.83 (95%CI 0.75-0.93), P=0.001). Conclusion: This study supports the notion that statin use is protective regarding breast cancer-specific mortality in agreement with previous Scandinavian studies, although less so with British studies. These disparities should be investigated further. Citation Format: Borgquist S, Broberg P, Olsson H. Statin use and breast cancer survival – a Swedish nationwide study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-13-03.

Association between unilateral or bilateral mastectomy and breast cancer death in patients with unilateral ductal carcinoma.

BackgroundUtilization of bilateral mastectomy for unilateral breast cancer is increasing despite cost and surgical risks with conflicting reports of survival benefit. Current studies evaluating death after bilateral mastectomy have included patients treated both with breast conservation therapy and unilateral mastectomy. In this study, we directly compared breast cancer–specific death of patients who underwent bilateral or unilateral mastectomy for unilateral breast cancer using a matched cohort analysis.MethodsThis was an observational study of women diagnosed with unilateral breast cancer from 1998 through 2002, using the Surveillance, Epidemiology, and End Results (SEER) database. A 4-to-1 matched cohort of patients was selected including 14,075 patients. Mortality of the groups was compared using Cox proportional hazards models for cause-specific death.ResultsA total of 41,510 patients diagnosed with unilateral breast cancer were included. Unilateral mastectomy was performed in 93% of patients, while bilateral mastectomy was performed in the remaining 7% of patients. When 4-to-1 matching was performed, 11,260 unilateral mastectomy and 2,815 bilateral mastectomy patients were included. Patients with bilateral mastectomy did not have a significantly lower hazard of breast cancer–specific death when compared with patients with unilateral mastectomy (hazard ratio: 0.92 vs 1.00, p=0.11).ConclusionBilateral mastectomy did not provide a clinically or statistically significant breast cancer–specific mortality benefit over unilateral mastectomy based on a matched cohort analysis of a nationwide population database. These findings should be interpreted in the context of patient preference and alternative benefits of bilateral mastectomy.

End-of-life prescribing of aspirin in patients with breast or colorectal cancer

ObjectivesThe aim of this study was to evaluate the influence of an approaching cancer death on end-of-life aspirin use, a frequently prescribed medication for cardiovascular disease prevention.MethodsThis study was conducted...

Body mass index, PAM50 subtype, recurrence, and survival among patients with nonmetastatic breast cancer.

Studies of obesity and survival among patients with breast cancer produce conflicting results, possibly because of heterogeneity by molecular subtype. This study examined whether the association of body mass index (BMI) at diagnosis with breast cancer recurrence and survival varied across subtypes defined by PAM50 (Prediction Analysis of Microarray 50) gene expression. Included were 1559 Kaiser Permanente Northern California members ages 18 to 79 years who had PAM50 assays and were diagnosed with American Joint Committee on Cancer stage I through III breast cancer from 1996 to 2013. Patients reported weight and height. Cox regression models were adjusted for age, menopause, race/ethnicity, stage, and chemotherapy. Over a median of 9 years (maximum, 19 years), 378 women developed recurrent disease, and 312 died from breast cancer. Overall, BMI was not associated with breast cancer recurrence or survival when controlling for subtype (eg, the hazard ratio per 5 kg/m2 of BMI was 1.05 [95% confidence interval, 0.95-1.15] for breast cancer-specific death). However, associations varied by subtype. Among women with luminal A cancers, those who had class II/III obesity, but not class I obesity or overweight, had worse outcomes. When women who had a BMI ≥35 kg/m2 were compared with those who had a BMI from 18.5 to <25 kg/m2 , the hazard ratio was 2.24 (95% confidence interval,1.22-4.11) for breast cancer-specific death and 1.24 (95% confidence interval, 1.00-1.54) for recurrence. There was no association within luminal B, basal-like or human epidermal growth factor over-expressing subtypes. Among patients who had accurately classified breast cancer subtypes based on gene expression, a BMI ≥35 kg/m2 was adversely associated with outcomes only among those who had luminal A cancers. Research is needed into whether tailoring recommendations for weight management to tumor characteristics will improve outcomes. Cancer 2017;123:2535-42. © 2017 American Cancer Society.

Real-world impact of non-breast cancer-specific death on overall survival in resectable breast cancer.

The real-world occurrence rate of non-breast cancer-specific death (non-BCSD) and its impact on patients with breast cancer are poorly recognized. Women with resectable breast cancer from 1990 to 2007 in the Surveillance, Epidemiology, and End Results database (n = 199,963) were analyzed. The outcome events of breast cancer were classified as breast cancer-specific death (BCSD), non-BCSD, or survival. Binary logistics was used to estimate the occurrence rates of non-BCSD and BCSD with different clinicopathological factors. The Gray method was used to measure the cumulative incidence of non-BCSD and BCSD. The ratio of non-BCSDs to all causes of death and stacked cumulative incidence function plots were used to present the impact of non-BCSD on overall survival (OS). Models of Cox proportional hazards regression and competing risk regression were compared to highlight the suitable model. There were 12,879 non-BCSDs (6.44%) and 28,784 BCSDs (14.39%). The oldest age group (>62 years), black race, and a single or divorced marital status were associated with more non-BCSDs. With adjustments for age, a hormone receptor-positive (HoR+) status was no longer related to increased non-BCSDs. In patients with grade 1, stage I disease and an HoR+ status as well as the oldest subgroup, a great dilution of non-BCSD on all causes of death could be observed, and this led to incorrect interpretations. The inaccuracy, caused by the commonly used Cox proportional hazards model, could be corrected by a competing risk model. OS was largely impaired by non-BCSD during early breast cancer. For some future clinical trial planning, especially for the oldest patients and those with HoR+ breast cancer, non-BCSD should be considered a competing risk event. Cancer 2017;123:2432-43. © 2017 American Cancer Society.

Abstract P4-12-02: Serum-triglycerides among triple negative breast cancer patients as a biomarker of poor outcome

Abstract Backgound: Obesity and related metabolic imbalances, including increased activity of free fatty acids, may promote tumor growth and metastasis. Fatty acids are mainly stored as triacylglycerols. Yet, the role of serum-triglycerides on breast cancer prognosis is still undefined. Methods: A population based survival study among 575 breast cancer patients identified within the Tromsø study during 1979-2008, was conducted. Pre-diagnostic serum triglycerides, high density lipoprotein-cholesterol, total cholesterol, height and weight were measured. Histopathological and clinical data were obtained from medical records, and hormone receptor, HER2 status, and Ki-67 were re-analyzed on tissue microarray blocks. Multivariate Cox proportional Hazard regression models were used to study the associations between patient characteristics including s-triglycerides, and breast cancer survival. Results: Among 575 women with invasive breast cancer (stage 1-3), a total of 87 women were diagnosed with triple negative breast cancer (TNBC). Patients diagnosed with TNBC, compared to non-TNBC, were likely to be younger at diagnosis (55.3 vs 57.9 years, p=0.061), they had larger tumors (29.7 mm vs 22.5 mm, p=0.001), and higher Ki-67 (31.1% vs 15.9%, p&amp;lt;0.001). After a mean follow-up of 8.4 years, TNBC patients with above median levels of s-triglycerides (&amp;gt; 0.98mmol/L) compared to TNBC patients with below median levels of s-triglycerides (≤ 0.98mmol/L) had 3.0 times higher risk for breast cancer recurrence or breast cancer specific death (HR 3.02, 95% CI 1.21-7.55), and 3.4 times higher overall mortality risk (HR 3.41, 95% CI 1.38-8.45). Among the TNBC patients, women with above median s-triglycerides had 15% lower 5-year disease-free survival (76% vs 91%) and 18% lower 5-year overall survival (74% vs 92%) compared to women with below median s-triglycerides. Conclusions: Our results strongly support s-triglycerides as an important biomarker for breast cancer outcomes among triple negative breast cancer patients. Table 1: Multivariable adjusted Hazard Ratios (HRs) for incidence breast cancer recurrence or breast cancer specific death, and incidence overall mortality by pre-diagnostic serum-triglycerides among non-triple negative breast cancer (TNBC) and TNBC patients Non-TNBC, n=488 TNBC, n=87 Recurrence or breast cancer specific death (n=90)Overall mortality (n=104) Recurrence or breast cancer specific death (n=24)Overall mortality (n=33) nHR (95% CI)HR (95% CI)nHR (95% CI)HR (95% CI)s-Triglycerides Median ≤ 0.98 mmol/l2571.001.00431.001.00&amp;gt; 0.98 mmol/l2310.87 (0.56-1.35)1.06 (0.70-1.62)443.02 (1.21-7.55)3.41 (1.38-8.45) Tertiles ≤ 0.82 mmol/l1731.001.00261.001.000.83 – 1.22 mmol/l1660.74 (0.44-1.23)0.81 (0.49-1.36)311.37 (0.38-4.98)0.98 (0.31-3.08)≥ 1.23 mmol/l1490.88 (0.50-1.54)1.17 (0.66-1.96)306.63 (1.64-19.3)3.87 (1.52-12.0)p-trend 0.4950.357 0.0050.007 Multivariate Cox proportional Hazard regression model. Adjusted for BMI and age at attendance (continuous), age at diagnosis (continuous), breast cancer stage at diagnosis (categorical), and current smoking (categorical). Abbreviation: CI, confidence interval; n, number of cases; TNBC, triple negative breast cancer Citation Format: Lofterød T, Mortensen ES, Nalwoga H, Wilsgaard T, Frydenberg H, Risberg T, Eggen AE, McTiernan A, Aziz S, Wist EA, Reitan JB, Akslen LA, Thune I. Serum-triglycerides among triple negative breast cancer patients as a biomarker of poor outcome [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-12-02.

Abstract P5-10-08: Estrogen receptor quantitative measures and differences in breast cancer survival

Abstract P5-10-08: Estrogen receptor quantitative measures and differences in breast cancer survival

The impact of nodal micrometastasis on mortality among women with early-stage breast cancer.

The clinical significance of nodal micrometastasis is debated. Our primary objective was to determine whether, among women with early-stage breast cancer, regional lymph node micrometastasis is an independent risk factor for mortality. The secondary objective was to identify subgroups of women who have the highest risk of death from early-stage breast cancer with micrometastases. 206,625 women diagnosed with early-stage breast cancer (IA, IB, and IIA) from 2004 to 2012 were identified in the Surveillance, epidemiology, and end results database. Nodal status was classified as node-negative, isolated-tumor cells, micrometastases, and macrometastases. Women were classified into eight ethnic groups. Logistic regression was performed to estimate the odds ratio of being diagnosed with micrometastases. The Cox proportional hazard model was used to estimate the hazard ratio (HR) of breast cancer-specific death associated with micrometastases for each ethnic group. The 8-year breast cancer-specific survival was 96.6% for women with node-negative breast cancers and was 94.6% for women with micrometastases (adjusted HR 1.49; 95% CI 1.31-1.69; P<.001). Among women with micrometastases, the 8-year breast cancer-specific survival was 95.1% for white women and was 90.6% for black women (HR 1.80; 95% CI 1.29-2.52; P=.0006). Nodal micrometastasis is an independent risk factor for breast cancer mortality among women with early-stage breast cancer. Black women are more likely to die from breast cancer with micrometastases than white women.

Statin use and breast cancer survival: a nationwide cohort study in Scotland.

BackgroundPreclinical evidence suggests that statins could delay cancer progression. Previous epidemiological findings have been inconsistent and some have been limited by small sample sizes, as well as certain time-related biases. This study aimed to investigate whether breast cancer patients who were exposed to statins had reduced breast cancer-specific mortality.MethodsWe conducted a retrospective cohort study of 15,140 newly diagnosed invasive breast cancer patients diagnosed from 2009 to 2012 within the Scottish Cancer Registry. Dispensed medication usage was obtained from linkages to the Scottish Prescribing Information System and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Using time-dependent Cox regression models, hazard ratios (HR) and 95 % confidence intervals (CI) were calculated for the association between post-diagnostic exposure to statins (including simvastatin) and breast cancer-specific mortality. Adjustments were made for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of aspirin.ResultsA total of 1,190 breast cancer-specific deaths occurred up to January 2015. Overall, after adjustment for potential confounders, there was no evidence of an association between statin use and breast cancer-specific death (adjusted HR 0.93, 95 % CI 0.77, 1.12). No significant associations were observed in dose–response analyses or in analysis of all-cause mortality. For simvastatin use specifically, a weak non-significant reduction in breast cancer-specific mortality was observed compared to non-users (adjusted HR 0.89, 95 % CI 0.73, 1.08). Statin use before diagnosis was weakly associated with a reduction in breast cancer-specific mortality (adjusted HR 0.85, 95 % CI 0.74, 0.98).ConclusionOverall, we found little evidence of a protective association between post-diagnostic statin use and cancer-specific mortality in a large nation-wide cohort of breast cancer patients. These findings will help inform the decision whether to conduct randomised controlled trials of statins as an adjuvant treatment in breast cancer.

TACC2 (transforming acidic coiled-coil protein 2) in breast carcinoma as a potent prognostic predictor associated with cell proliferation.

Transforming acidic coiled‐coil protein 2 (TACC2) belongs to TACC family proteins and involved in a variety of cellular processes through interactions with some molecules involved in centrosomes/microtubules dynamics. Mounting evidence suggests that TACCs is implicated in the progression of some human malignancies, but significance of TACC2 protein in breast carcinoma is still unknown. Therefore, in this study, we examined the clinical significance of TACC2 in breast carcinoma and biological functions by immunohistochemistry and in vitro experiments. Immunohistochemistry for TACC2 was performed in 154 cases of invasive ductal carcinoma. MCF‐7 and MDA‐MB‐453 breast carcinoma cell lines were transfected with small interfering RNA (siRNA) for TACC2, and subsequently, cell proliferation, 5‐Bromo‐2′‐deoxyuridine (BrdU), and invasion assays were performed. TACC2 immunoreactivity was detected in 78 out of 154 (51%) breast carcinoma tissues, and it was significantly associated with Ki‐67 LI. The immunohistochemical TACC2 status was significantly associated with increased incidence of recurrence and breast cancer‐specific death of the patients, and multivariate analyses demonstrated TACC2 status as an independent prognostic factor for both disease‐free and breast cancer‐specific survival. Subsequent in vitro experiments showed that TACC2 significantly increased the proliferation activity of MCF‐7 and MDA‐MB‐453. These results suggest that TACC2 plays an important role in the cell proliferation of breast carcinoma and therefore immunohistochemical TACC2 status is a candidate of worse prognostic factor in breast cancer cases.

Benefit of adjuvant radiotherapy after breast-conserving therapy among elderly women with T1-T2N0 estrogen receptor-negative breast cancer.

The purpose of the current study was to evaluate the impact of radiotherapy (RT) among women aged ≥ 70 years with T1-2N0 estrogen receptor (ER)-negative breast cancer using Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked data. The study included 3432 women, 2850 of whom received and 582 of whom did not receive RT after breast-conserving surgery. Outcomes were estimated by the cumulative incidence method and compared with the Gray test. The Fine and Gray subdistribution hazard regression models were used to assess the impact of RT and other variables. Women who received RT were more commonly aged <75 years (42% vs 16%), had T1 tumors (78% vs 65%), ductal carcinoma histology (91% vs 88%), a Charlson-Deyo Comorbidity Index of 0 (41% vs 25%), and had received chemotherapy (29% vs 12%). The 5-year cumulative incidence of mastectomy and breast cancer-specific death for patients who received versus those did not receive adjuvant RT was 4.9% and 8.3% versus 10.8% and 24.1%, respectively (P<.001). On multivariable analysis, the omission of RT was found to be an independent predictor of an increased risk of mastectomy (hazard ratio, 2.33; 95% confidence interval, 1.56-3.49). Among women aged ≥ 80 years or with T1N0 tumors, the mastectomy incidence with or without receipt of RT was 3.4% vs. 6.9%, and 5.3% vs 7.7%, respectively. The use of adjuvant RT after breast-conserving surgery in older women with T1-2N0 estrogen receptor-negative breast cancer is associated with a reduced incidence of future mastectomy and breast cancer death. The magnitude of benefit may be small for women aged ≥80 years or those with T1 tumors. Cancer 2016;122:3059-3068. © 2016 American Cancer Society.

Delaying chemotherapy after surgery in patients with breast cancer reduces survival.

Delaying chemotherapy more than 90 days after surgery for breast cancer may significantly increase the risk of death, particularly among patients with triple-negative breast cancer (TNBC), according to a new study from The University of Texas MD Anderson Cancer Center in Houston.1 Currently, there are no guidelines recommending the optimal time to the initiation of adjuvant chemotherapy. For certain patients, the Centers for Medicare and Medicaid Services uses the administration of adjuvant chemotherapy within 120 days of diagnosis as a quality metric. The University of Texas MD Anderson Cancer Center and 10 other cancer hospitals are now reporting on this metric. The authors of the current study found that the factors contributing to delayed treatment were socioeconomic status, insurance coverage, and ethnicity. They found that patients who initiate chemotherapy more than 90 days after surgery are 34% more likely to die within 5 years, and patients with TNBC who delay treatment have a 53% increased risk of death. Lead author Mariana Chavez MacGregor, MD, assistant professor of health services research and breast medical oncology, notes that although adjuvant chemotherapy given after primary surgery has been shown to decrease the risk of recurrence and death, delaying the start of it may allow small remnants of the tumor to grow or become drug-resistant. The population-based study assessed data from 24,823 patients with stage I to III invasive breast cancer diagnosed between January 1, 2005, and December 31, 2010, who were treated with adjuvant chemotherapy. The study is the largest investigating delayed chemotherapy initiation with contemporary treatment regimens. Investigators found that compared with patients starting chemotherapy in the first month after surgery, those who initiated the treatment between 30 and 90 days after surgery did not have adverse outcomes. However, those patients who started chemotherapy 90 days after surgery had a statistically significant increase in the risk of death and breast cancer-specific death. The latter patients (9.8% of all participants) were 34% more likely to die within 5 years and 27% more likely to die from breast cancer in that time frame in comparison with patients who received chemotherapy within 30 days of surgery. Researchers also analyzed the data by breast cancer subtype. For patients with TNBC, a delay of more than 90 days was associated with a 53% increase in the risk of death. There was no significant effect from delay for those with hormone receptor–positive or human epidermal growth factor receptor 2–positive breast cancers. As a result of the findings, study senior author Sharon Giordano, MD, MPH, professor and chair of health services research, concludes that timely initiation of chemotherapy is particularly important for patients with TNBC. Among the factors contributing to the delayed administration of chemotherapy were increased age, reconstructive surgery, and low sociodemographic status. Patients without private insurance and those of Hispanic or African American descent were more likely to experience treatment delays. Patients receiving care at NCI-designated cancer centers had a 34% lower risk of death in comparison with those treated elsewhere. The authors note that in most clinical situations, starting chemotherapy within 3 months is more than feasible. All patients with breast cancer who receive adjuvant chemotherapy should do so within 90 days of surgery or 120 days of diagnosis, say the authors.

Infection-related hospitalizations in breast cancer patients: Risk and impact on prognosis

Infections are a common cause of hospitalization in breast cancer patients. We studied the risk, clinical characteristics and outcomes of infection-related hospitalizations in this patient population. A Swedish registry-based study including 8338 breast cancer patients diagnosed between 2001 and 2008, followed prospectively for infection-related hospitalizations until 2010. Standardized incidence ratios (SIRs) were calculated using background rates from the general female population. Associations with clinical characteristics and mortality were analyzed using flexible parametric survival models. In total, 720 patients experienced an infection-related hospitalization during a median follow-up of 4.9 years. Infection rates were highest within the first year of diagnosis (SIR=5.61, 95% CI; 4.98-6.32), and site-specific risks were most pronounced for sepsis (SIR=3.14, 95% CI; 2.66-3.71) and skin infections (SIR=2.80, 95% CI; 2.24-3.50). Older age at diagnosis, comorbidities, markers of tumor aggressiveness, chemotherapy and axillary node dissection were independent predictors of infectious disease risk. Infection-related hospitalizations were also independently associated with overall and breast cancer-specific death. A significant number of breast cancer patients are hospitalized with an infection following diagnosis, which in turn predicts poor prognosis. The risk profile of infection-related hospitalizations is multifactorial, including patient, tumor and treatment-related factors.

Nomograms to estimate long-term overall survival and breast cancer-specific survival of patients with luminal breast cancer.

Luminal breast cancer constitutes a group of highly heterogeneous diseases with a sustained high risk of late recurrence. We aimed to develop comprehensive and practical nomograms to better estimate the long-term survival of luminal breast cancer.Patients with luminal breast cancer diagnosed between 1990 and 2006 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into the training (n = 87,867) and validation (n = 88,215) cohorts. The cumulative incidence function (CIF) and a competing-risks model were used to estimate the probability of breast cancer-specific survival (BCSS) and death from other causes. We integrated significant prognostic factors to build nomograms and subjected the nomograms to bootstrap internal validation and to external validation.We screened 176,082 luminal breast cancer cases. The 5- and 10-year probabilities of overall death were 0.089 and 0.202, respectively. The 5- and 10-year probabilities of breast cancer-specific mortality (BCSM) were 0.053 and 0.112, respectively. Nine independent prognostic factors for both OS and BCSS were integrated to construct the nomograms. The calibration curves for the probabilities of 5- and 10-year OS and BCSS showed excellent agreement between the nomogram prediction and actual observation. The C-indexes of the nomograms were high in both internal validation (0.732 for OS and 0.800 for BCSS) and external validation (0.731 for OS and 0.794 for BCSS).We established nomograms that accurately predict OS and BCSS for patients with luminal breast cancer. The nomograms can identify patients with higher risk of late overall mortality and BCSM, helping physicians in facilitating individualized treatment.

Body mass index and survival after diagnosis of invasive breast cancer: a study based on the Japanese National Clinical Database-Breast Cancer Registry.

Few studies have reported the association between body mass index (BMI) and outcome among Asian breast cancer patients. We analyzed data for 20,090 female invasive breast cancer patients who had been followed‐up for a median period of 6.7 years entered in the National Clinical Database–Breast Cancer Registry between 2004 and 2006. We used mainly the WHO criteria for BMI (kg/m2) categories; <18.5 (underweight), ≥18.5–<21.8 (reference), ≥21.8–<25, ≥25–<30 (overweight), and ≥30 (obese). We divided normal weight patients into two subgroups because this category includes many patients compared to others. The timing of BMI measurement was not specified. The Cox proportional hazards model and cubic spline regression were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Smoking, alcohol, and physical activity were not controlled. A total of 1418 all‐cause, 937 breast cancer–specific deaths, and 2433 recurrences were observed. Obesity was associated with an increased risk of all‐cause (HR: 1.46; 95% CI: 1.16–1.83) and breast cancer–specific death (HR: 1.47; 95% CI: 1.11–1.93) for all patients, and with all‐cause (HR: 1.47; 95% CI: 1.13–1.92) and breast cancer–specific death (HR: 1.58; 95% CI: 1.13–2.20) for postmenopausal patients. Being underweight was associated with an increased risk of all‐cause death for all (HR: 1.41; 95% CI: 1.16–1.71) and for postmenopausal patients (HR: 1.45; 95% CI: 1.15–1.84). With regard to subtype and menopausal status, obesity was associated with an increased risk of breast cancer–specific death for all cases of luminal B tumor (HR: 2.59; 95% CI: 1.51–4.43; Pheterogeneity of Luminal B vs. Triple negative = 0.016) and for postmenopausal patients with luminal B tumor (HR: 3.24; 95% CI: 1.71–6.17). Being obese or underweight is associated with a higher risk of death among female breast cancer patients in Japan.

Abstract P2-07-03: Nomograms to estimate long-term overall survival and breast cancer-specific survival of patients with luminal breast cancer

Abstract Purpose Luminal breast cancer (estrogen receptor [ER] and/or progesterone receptor [PR] positive) represents approximately two-thirds of all breast cancer. This type of cancer constitutes a group of highly heterogeneous diseases with a sustained high risk of late recurrence. In this study, we aimed to develop comprehensive and practical nomograms for the first time to better estimate the long-term survival of luminal breast cancer. Thus, those patients with high risk of late recurrence and poor prognosis could be screened out and individualized treatments can be applied. Methods Patients with luminal breast cancer diagnosed between 1990 and 2006 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database, and randomly divided into the training (n=87,867) and validation (n=88,215) cohorts. The inclusion criteria we used to identify eligible patients were as follows: female; aged 18 to 79 years old at diagnosis; known time of diagnosis from January 1, 1990, to December 31, 2006; unilateral breast cancer; breast cancer as the first and only cancer diagnosis; diagnosis not obtained from a death certificate or autopsy; surgical treatment with either mastectomy or breast-conserving surgery; pathologic confirmation of invasive carcinoma; AJCC stages I-III; histological grade I-III and known ER and PR statuses. Patients with inflammatory breast cancer or Paget's disease and lack of data on the above inclusion criteria were also excluded. Univariate and multivariate survival analyses were applied to identify prognostic factors for overall survival (OS). The cumulative incidence function (CIF) and a competing-risks model were used to estimate the probability of breast cancer-specific survival (BCSS) and death from other causes. We integrated significant prognostic factors to build nomograms, and subjected the nomograms to bootstrap internal validation and external validation. Results We screened 176,082 luminal breast cancer cases. The mean age at diagnosis was 57.5 years, and mean survival time was 107.4 months. By the end of the last follow-up, 36,911 (21.0%) patients had died, including 17,855 (10.1%) died from breast cancer and 19,056 (10.8%) from other causes. The 5- and 10-year probabilities of overall death were 0.089 and 0.202, respectively. The 5- and 10-year probabilities of breast cancer specific-mortality (BCSM) were 0.053 and 0.112, respectively. Independent prognostic factors for both OS and BCSS were integrated to construct the nomograms, including age at diagnosis, race, tumor size, histology, grade, positive lymph nodes, ER/PR status and radiation. The calibration curves for the probabilities of 5- and 10-year OS and BCSS showed excellent agreement between the nomogram prediction and actual observation. The C-indexes of the nomograms were high in both internal validation (0.732 for OS and 0.800 for BCSS) and external validation (0.731 for OS and 0.794 for BCSS). Conclusion We established and validated nomograms that accurately predict OS and BCSS of luminal breast cancer based on a large, population-based cohort with long-term follow-up. The nomograms can identify patients with higher risk of late overall mortality and BCSM, helping physicians in facilitating individualized treatment. Citation Format: Sun W, Jiang Y-Z, Liu Y-R, Ma D, Shao Z-M. Nomograms to estimate long-term overall survival and breast cancer-specific survival of patients with luminal breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-07-03.

Abstract P1-09-05: Survival disparities: Quality of care apparently not the answer

Abstract Introduction: In New Mexico (NM), Hispanic women have a 1.6-fold increased risk of breast cancer-specific death compared to non-Hispanic white women. In previous studies, race/ethnic minority women have been less likely to receive recommended adjuvant treatments, including radiation in women undergoing breast conservation, and hormonal therapy. Objective: To determine whether non-receipt of recommended therapies contributed to disparate survival. Methods: We conducted a case-cohort study of breast-cancer-specific survival within a population-based cohort of first invasive breast cancer diagnosed in white females from 1997-2009 in six NM counties, identified through Surveillance Epidemiology End Results (SEER). We selected fifteen percent of all women diagnosed with breast cancer and all breast cancer deaths. After IRB approval, data were collected from comprehensive medical chart reviews, supplemented by SEER information. Receipt of standard of care, vs. not, was defined based on age, diagnosis year and tumor characteristics, according to changes in treatment guidelines. Women who had a reported contraindication or refused therapy were omitted from assessment of quality of care for that therapy. Cox proportional hazards models for case-cohort were conducted using weighted estimates, with calculation of robust variance and hazard ratios (HR) and 95% confidence intervals (CI), using an alpha level of .05. Analyses were restricted to women of age 70 or less who survived at least 12 months. The proportional hazards assumption was verified by Schoenfeld residuals. All analyses were adjusted for age. Results: Comprehensive medical records reviews were completed for 91% of eligible women (674 cohort members, 519 breast cancer deaths; median follow up 7.8 years). All others were omitted from analysis. Of women eligible for guideline-based treatment, receipt of guideline-appropriate therapy did not differ by Hispanic ethnicity for any treatment, and Hispanic women were slightly more likely overall to receive appropriate therapy (difference not significant). Among guideline-eligible women, at least 91% received radiotherapy, 78% received chemotherapy, 82% received endocrine therapy, and 89% received anti-HER2 targeted agents. After adjustment for other treatment, lack of receipt of guideline-appropriate therapy was related to an increased risk of breast cancer death for endocrine (HR 1.76; 95% CI 1.09-2.84) and radiation therapy (HR 2.05; 95% CI 1.14-3.69). The few HER2-positive women not treated precluded further assessment. After accounting for endocrine and radiation therapy the survival disparity HR of 1.6 in Hispanic women was reduced to 1.57 suggesting only 2% of the disparity was due to differences in receipt of these treatments. Conclusion: Limitations include likely undercounts of appropriate therapy, thus proportions cited are minimal estimates. Appropriate therapy includes only documented receipt as therapy completion could not always be assessed. Hispanic women have a disproportionately higher breast cancer mortality despite apparently receiving adjuvant therapies to a similar degree as non-Hispanic white women. Equalizing standard of care and attempting to reduce treatment disparities may not be sufficient to address the disproportionate mortality in Hispanic women. Citation Format: Friend SC, Royce ME, Kang H, Lomo L, Barry M, Wiggins C, Prossnitz E, Hill DA. Survival disparities: Quality of care apparently not the answer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-09-05.

Programmed death ligand 1 expression in triple‐negative breast cancer is associated with tumour‐infiltrating lymphocytes and improved outcome

Triple-negative breast cancer (TNBC) patients generally have a poor outcome; there is a pressing need to identify more effective therapeutic strategies. Clinical trials targeting programmed death 1/programmed death ligand 1 (PD1/PDL1) in melanoma and non-small-cell lung cancer have reported high response rates, and tumoral PDL1 expression has been suggested as a potential biomarker to enrich for patient response to these treatments. There are only very limited data to date reporting the expression of PDL1 in TNBC. PDL1 immunohistochemistry was performed on 161 primary TNBCs and assessed in the tumour as well as immune cells in the stromal compartment. PDL1 expression was very common in TNBC, expressed in the tumour cell membrane (64%), cytoplasm (80%) and stromal (93%) cellular compartments. Cytoplasmic tumoral expression of PDL1 was associated with a lower risk of breast cancer-specific death [hazard ratio (HR) 0.45, P = 0.035] while stromal PDL1 expression was associated with a lower rate of deaths from all causes (HR 0.305, P = 0.0042). Membranous expression of PDL1 was not associated with outcome. While both PDL1 expression and tumour-infiltrating lymphocytes were associated with a better outcome, only lymphovascular invasion and high tumour-infiltrating lymphocytes were independently prognostic for breast cancer-specific death. While PDL1 expression is frequent in TNBC, it was not independently prognostic. There were differences in outcome depending on the cellular compartment of PDL1 expression. These data provide further impetus for investigating the utility of immune checkpoint therapies in TNBC, given the clinical significance of tumour-infiltrating lymphocytes (TILs) and PDL1 expression in this cohort.

Progression of breast cancer following locoregional ipsilateral recurrence: importance of interval time.

Background:Studies comparing prognosis of breast cancer (BC) patients with and without locoregional recurrence (LR) present conflicting results. We aimed to improve our understanding of the impact of LR on prognosis by examining a large cohort of patients treated at Guy's and St Thomas' NHS Foundation Trust.Methods:Risk factors associated with BC-specific death were investigated using Cox proportional hazards regression in 5199 women diagnosed between 1975 and 2007. Breast cancer-specific death following LR was assessed with Poisson regression.Results:Overall, 552 women (11%) developed LR, with a median follow-up time of 4.28 years. Known factors associated with BC-specific death (tumour stage, grade, and nodal status) were of significance in our data. Women with a shorter disease-free interval had a worse prognosis. For instance, the HR for BC-specific death among women undergoing mastectomy with an LR 0.5–1 year after diagnosis of their primary tumour was 6.67 (95% CI: 3.71–11.99), when compared with women who did not experience LR.Conclusions:It often remains difficult to distinguish between a genuine LR and a new primary. The HRs for risk of BC-specific death following a second lesion suggest that they may act as a marker of systemic disease, large tumour burden, or depleted host defence. The clinically highly relevant impairment in prognosis calls for further research into the underlying mechanisms. We showed that for at least 15 years of follow-up, the prognosis in women following the occurrence of an LR may benefit from careful diagnostic and therapeutic management.

Breast Cancer Molecular Subtypes and Oxidative DNA Damage.

Oxidative stress is thought to play a major role in etiology of many cancers, including breast cancer. 8-hydroxy-2'deoxyguanosine (8-OHdG) is the most abundant marker of oxidative DNA damage. The aim of this study was to assess the extent of oxidative DNA damage in different breast cancer molecular surrogate subtypes to investigate the prognostic relevance and role of oxidative base lesion (8-OHdG) in the etiology of breast cancer. 8-OHdG expression was immunohistochemicaly studied on tissue microarrays constructed from 152 patients with invasive breast cancer. Expression was correlated with other prognostic factors, as well as different breast cancer molecular surrogate subtypes such as luminal A, luminal B [human epidermal growth factor receptor 2 (HER2) negative], luminal B (HER2 positive), HER2-enriched ad triple-negative tumors. Triple-negative breast carcinomas (TNBCs) were more frequently 8-OHdG negative compared with non-TNBCs (P=0.036). There was no statistically significant difference between 8-OHdG expression and other breast cancer molecular subtypes.In univariate analysis, there was no significant difference between 8-OHdG expression and breast cancer-specific death, although in multivariate analysis 8-OHdG overexpression was associated with better breast cancer-specific survival (BCSS) (odds ratio=0.04, 95% confidence interval, 0.002-0.62). In Cox regression analysis, patients with moderate and strong 8-OHdG expression had 0.9 times smaller breast cancer death hazard ratio than patients with negative 8-OHdG expression. Oxidative stress may have less impact in the pathogenesis of TNBCs compared with other surrogate breast cancer molecular subtypes. 8-OHdG may be a promising biomarker in the prediction of prognosis for breast cancer patients.