Adjuvant Breast Radiotherapy Improve Survival in Women With Heart Failure

BACKGROUND To date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast intraductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF). PATIENTS AND METHODS : We enrolled 294 women with left-breast IDC at clinical stages IA–IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score–weighted population to obtain hazard ratios (HRs). RESULTS In the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.60; 95% confidence interval [CI]: 0.44–0.94) was a significant independent prognostic factor for all-cause death (P = 0.0424), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.33 (0.24–0.71; P = 0.0017) and 0.37 (0.22–0.63; P = 0.0004), respectively, compared with the no adjuvant WBRT group. The aHR (95% CI) of breast cancer death for adjuvant WBRT was 0.54 (0.44–0.85; P = 0.0201) compared with no adjuvant WBRT group. CONCLUSION Adjuvant WBRT was associated with a decrease in all-cause death, breast cancer death, LRR, and DM in women with left IDC and HFrEF compared with no adjuvant WBRT.

Modeling risks of cardiovascular and cancer mortality following a diagnosis of loco-regional breast cancer

Background Many women with breast cancer also have a high likelihood of cardiovascular mortality, and while there are several cardiovascular risk prediction models, none have been validated in a cohort of breast cancer patients. We first compared the performance of commonly-used cardiovascular models, and then derived a new model where breast cancer and cardiovascular mortality were modeled simultaneously, to account for the competing risk endpoints and commonality of risk factors between the two events. Methods We included 20,462 women diagnosed with stage I–III breast cancer between 2000 and 2010 in Kaiser Permanente Northern California (KPNC) with follow-up through April 30, 2015, and examined the performance of the Framingham, CORE and SCOREOP cardiovascular risk models by area under the receiver operating characteristic curve (AUC), and observed-to -expected (O/E) ratio. We developed a multi-state model based on cause-specific hazards (CSH) to jointly model the causes of mortality. Results The extended models including breast cancer characteristics (grade, tumor size, nodal involvement) with CVD risk factors had better discrimination at 5-years with AUCs of 0.85 (95% CI 0.83, 0.86) for cardiovascular death and 0.80 (95% CI 0.78, 0.87) for breast cancer death compared with the existing cardiovascular models evaluated at 5 years AUCs ranging 0.71–0.78. Five-year calibration for breast and cardiovascular mortality from our multi-state model was also excellent (O/E = 1.01, 95% CI 0.91–1.11). Conclusion A model incorporating cardiovascular risk factors, breast cancer characteristics, and competing events, outperformed traditional models of cardiovascular disease by simultaneously estimating cancer and cardiovascular mortality risks.

548Cancer treatment and survival disparity in South Australia women with invasive breast cancer during 2000-2014

Background Survival improvement from breast cancer has been attributed mostly to treatment advances and earlier cancer detection. This study was to investigate cancer treatment and the association with survival. Methods A total of 13494 female patients with invasive breast cancer recorded on the South Australia Cancer Registry in 2000-2014 were included. Cancer treatments within 12 month following diagnosis were identified from linked cancer registry and other medical registries. Study factors included demo sociographic, tumour profile and comorbidity. Adjusted odds ratios and sub hazard ratios were reported on treatment and survival disparity respectively. Results 98% patients were treated with one or more treatment types. 56% had conserving surgery. Systemic treatment was received by 72%. Older patients with advanced cancer were less likely to have any treatment. Women in the most socioeconomically advantaged area were less likely to have combined mastectomy and conservative surgery (aOR 0.73, 95% CI 0.54-0.98), but more likely to have systemic treatment (aOR 1.44, 95% CI 1.26-1.64). Other factors such as country of birth, residential socioeconomic status, cancer differentiation, and diagnosis period differed in their associations with treatment type. Having conserving surgery predicted the lowest breast cancer death (adjusted SHR 0.31, 95% CI 0.26-0.36) compared to no surgery. Conclusions Breast cancer patients underwent varied treatment types with different impact on breast cancer mortality. Key messages Patients undergoing conserving surgery were at the lowest risk of the cancer death.

Medicare Coverage Improves Mortality Outcomes in Regions of Poverty in United States

Objectives: Access to care and poverty have been associated with a higher risk of breast cancer, but their impact on breast cancer death has not been fully evaluated. We hypothesized that analysis of data from a large database would further elucidate the association between socioeconomic status and breast cancer mortality. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify cases of invasive ductal carcinoma diagnosed between 2006-2011, as well as data reflecting the presence or absence of a breast cancer death within five years. Two age groups, 40-64 year old women, and 65+ year old women, were analyzed. From the American Community Survey were acquired annual county level hospital rates, ambulatory care facility rates, nursing/residential care facility rates, rural business rates, population densities, and counts of women in the age groups of interest. Results: With respect to poverty rates, incidence based mortality rates for 40-64 year old women were 13% (99% CI 3%, 25%) higher for counties in the third quartile and 19% (7%, 35%) higher for counties in the fourth quartile (p < 0.01) than for counties in the first quartile; counties in the second quartile did not show higher incidence mortality rates (p > 0.01). Mortality rates for 65+ year old women did not differ among poverty rate quartiles (p > 0.01 for each assessment). A 50% increase in hospitals per 100,000 persons was associated with 8% (5%, 11%) and 5% (1%, 8%) increases in mortality rates for 40-64 y and 65+ y women, respectively, likely reflecting better ascertainment of causes of death at hospitals. Impacts of differences in other rates and population density were not detected (p > 0.01 for each analysis). Conclusion: Counties with higher poverty rates have increased breast cancer mortality rates for 40-64 y women, but not for 65+ y women. Universal coverage associated with Medicare is associated with the absence of an apparent effect of poverty upon breast cancer mortality.

523Use of beta blockers and death from breast cancer in New Zealand breast cancer patients

Background Beta blockers (BB), used for a range of cardiovascular indications, have been associated with improved, worsened, and unchanged breast cancer outcomes in previous studies. This study examines the association between the use of BBs and death from breast cancer in a large, representative sample of New Zealand women. Methods Women diagnosed with a first primary breast cancer between 2007 and 2016 were identified from four population-based regional NZ breast cancer registries and linked to pharmaceutical data, hospital discharges, and death records. The median follow up time was 4.51 years. Cox proportional hazard models were used to assess the hazard of breast cancer specific death (BCD) associated with post-diagnostic BB use. Results Of the 14,976 women included in analysis, 21% used a BB after diagnosis. Although not significant, beta blocker use increased the risk of BCD (adjusted hazard ratio: 1.08; 95% CI: 0.93-1.26). The increased risk was seen only in those with at least one cardiac condition, and was also reduced by lagging the exposure, suggesting effects of BB use close to the end of life. The increased risk was also confined to short term use (0-3 months). BB use for more than 1 year was associated with a decreased risk of BCD, and the risk steadily decreased to HR 0.53 (95% CI: 0.33-0.85) for use for 3+ years. Conclusions Any increased risk associated with BB use is likely to be due to a combination of confounding by indication and short-term use. Long-term BB use may confer some protection for BCD. Key messages The effect of beta blockers is difficult to separate from the indications for the drug. While there was no significant overall effect, there was a suggestion that beta blockers may be protective for breast cancer death with long-term exposure.

Effect of Postoperative Radiotherapy In Women With Localized Pure Mucinous Breast Cancer After Lumpectomy: A Population-Based Study

PurposePure mucinous breast cancer (PMBC) is a rare subtype of invasive breast cancer with favorable prognosis, in which the effect of postoperative radiotherapy remains unclear. We aimed to investigate the prognostic value of postoperative radiotherapy in women with localized PMBC after lumpectomy.MethodsWe conducted a retrospective cohort study to compare the effectiveness of postoperative radiotherapy (RT) and omitting postoperative radiotherapy (non-RT) in patients with first primary T1-2N0M0 (T ≤ 3cm) PMBC who underwent lumpectomy between 1998 and 2015 using the Surveillance, Epidemiology, and End Results (SEER) database. Breast cancer-specific survival (BCSS) was compared between RT and non-RT groups using Kaplan–Meier method and Cox proportional hazards regression model. Propensity score matching (PSM) was carried out to balance cohort baselines. In addition, an exploratory analysis was performed to verify the effectiveness of RT in subgroup patients. Results Overall, 5352(68.2%) and 2494(31.8%) eligible patients with tumor size ≤ 3cm localized PMBC received lumpectomy with postoperative RT and lumpectomy without postoperative RT respectively. The median follow-up duration was 92 months. The 15-year BCSS was 94.39% (95% CI, 93.08% to 95.35%) in the RT group versus 91.38% (95% CI, 88.86% to 93.35%) in the non-RT group (P < 0.001). The adjusted hazard ratio for BCSS was 0.64 (95%CI, 0.49 to 0.84; P = 0.001) for RT group versus non-RT group. After PSM, similar results were yielded. Adjuvant RT reduced the 15-year risk of breast cancer death from 7.92% to 6.15% (P = 0.039). The adjusted hazard ratio for BCSS were 0.66 (95%CI, 0.47 to 0.92; P = 0.014) for RT group versus non-RT group. The benefit of RT was well consistent across all subgroups.ConclusionAmong women with T1-2N0M0 (tumor size ≤ 3cm) PMBC, the addition of RT after lumpectomy was significantly associated with a reduced incidence of breast cancer death compared with non-RT, and the magnitude of benefit may be modest. This suggests that postoperative RT is recommended in the treatment of localized PMBC.

Detection and significance of small and low proliferation breast cancer

Objectives To determine the frequency and discuss possible implications of early breast cancer with particularly good prognosis and defined by tumor diameter and cell proliferation. Setting Detection of small and slowly growing tumors presents a challenge in breast cancer management, due to the risk of over-treatment. Here, we attempted to define a group of such tumors by combining small diameter (≤10 mm, T1ab tumors) with low tumor cell proliferation (≤10% Ki67 expression rate). These tumors were termed small low proliferation cancers (SLPC). Methods Two population-based cohorts were studied: a small research series ( n = 534), and a nation-wide registry-based series of prospectively collected routine data ( n = 8433). In the latter, we stratified by detection mode; screen-detected, interval, and breast cancers detected outside of screening. Patients were treated according to national guidelines at time of their diagnosis. For both cohorts, we compared tumor histopathology and risk of breast cancer death using a log-rank test for cases with SLPC versus non-SLPC. Results In the research series (median follow-up 151 months), the frequency of SLPC was 10% (54/534), with one breast cancer death compared with 78 among the remaining 480 cases of non-SLPC ( p = 0.008). In the registry series (median follow-up 42 months), the frequency of SLPC was 10% (854/8433), with five deaths compared to 187 among the remaining 7579 cases ( p = 0.0004). Conclusions SLPC was associated with very low risk of breast cancer death. Prospective randomized trials are needed to clarify whether less aggressive treatment could be a safe option for women with such early breast cancers.

Trends in breast cancer survival by race-ethnicity in Florida.

e18556 Background: Considerable efforts to improve disparities in breast cancer outcomes for underserved women have occurred over the past 3 decades. This study was conducted to evaluate trends in survival, by race-ethnicity, for women diagnosed with breast cancer in Florida over a 26-year period to assess potential improvement in racial-ethnic disparities. Methods: This was a retrospective cohort study of women diagnosed with invasive breast cancer in Florida between 1990-2015. Data were obtained from the Florida Cancer Data System. Women in the study were categorized according to race (white/black) and Hispanic ethnicity (yes/no) as non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic white (HW), and Hispanic black (HB). Cumulative incidence estimates of 5- and 10-year breast cancer death with 95% confidence intervals (CI) were obtained by race-ethnicity, according to diagnosis year. Subdistribution hazard models were used to obtain subdistribution hazard ratios (sHR) for the relative rate of breast cancer death accounting for competing causes. Results: Compared to NHW women, minority women were more likely to be younger, be uninsured or have Medicaid as health insurance, live in high poverty neighborhoods, have more advanced disease at diagnosis, have high grade tumors, have hormone receptor negative tumors, and receive chemotherapy as treatment. Minority women were less likely to receive surgery. Over the course of the study, breast cancer mortality decreased for all racial-ethnic groups, and racial-ethnic minorities had greater absolute and relative improvement in breast cancer survival for nearly all metrics compared to non-Hispanic white (NHW) women. However, for the most recent time period (2010-2015), black women still experienced significant survival disparities with non-Hispanic black (NHB) women having twice the rate of 5-year (sHR = 2.04: 95% CI; 1.91-2.19) and 10-year (sHR = 2.02: 95% CI; 1.89-2.16) breast cancer death. Conclusions: Despite efforts to improve disparities in breast cancer outcomes for underserved women in Florida, additional targeted approaches are needed to reduce the poorer survival in black (especially NHB) women. Our next step is to conduct a mediation analysis of the most important factors driving racial/ethnic disparities in breast cancer outcomes for women in Florida.

In modern times, how important are breast cancer stage, grade and receptor subtype for survival: a population-based cohort study

Background In breast cancer, immunohistochemistry (IHC) subtypes, together with grade and stage, are well-known independent predictors of breast cancer death. Given the immense changes in breast cancer treatment and survival over time, we used recent population-based data to test the combined influence of IHC subtypes, grade and stage on breast cancer death. Methods We identified 24,137 women with invasive breast cancer aged 20 to 74 between 2005 and 2015 in the database of the Cancer Registry of Norway. Kaplan-Meier curves, mortality rates and adjusted hazard ratios for breast cancer death were estimated by IHC subtypes, grade, tumour size and nodal status during 13 years of follow-up. Results Within all IHC subtypes, grade, tumour size and nodal status were independent predictors of breast cancer death. When combining all prognostic factors, the risk of death was 20- to 40-fold higher in the worst groups compared to the group with the smallest size, low grade and ER+PR+HER2− status. Among node-negative ER+HER2− tumours, larger size conferred a significantly increased breast cancer mortality. ER+PR−HER2− tumours of high grade and advanced stage showed particularly high breast cancer mortality similar to TNBC. When examining early versus late mortality, grade, size and nodal status explained most of the late (> 5 years) mortality among ER+ subtypes. Conclusions There is a wide range of risks of dying from breast cancer, also across small breast tumours of low/intermediate grade, and among node-negative tumours. Thus, even with modern breast cancer treatment, stage, grade and molecular subtype (reflected by IHC subtypes) matter for prognosis.