Breast Cancer Outcomes In Women Research Articles

Age has a U-shaped relationship with breast cancer outcomes in women: a cohort study.

Age is a significant determinant of susceptibility to breast cancer. Currently, the available evidence regarding the non-linear correlation between the age of diagnosis and the prognosis of breast cancer patients is contradictory. Insufficient data currently exist regarding the influence of age at diagnosis on the prognosis of breast cancer. The objective of our investigation was to examine the relationship between age at diagnosis and overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS). This retrospective cohort study included 1054 patients diagnosed with breast cancer between March 7, 2013 and December 31, 2019. The hazard ratios (HRs) and 95% confidence interval (CI) for OS, BCSS, DFS were assessed using Cox proportional hazard ratio models and restricted cubic splines (RCS). The study included 1054 breast cancer patients who met the criteria. With a median follow-up of 4.86 years, 71 patients (6.74%) died and 144 patients (13.66%) relapsed. After multivariable adjustment, age showed a U-shaped association with OS, BCSS, and DFS, with significantly higher risk at two ends, with age inflection points of 44, 44, and 41 years for OS, BCSS, and DFS, respectively. For OS, Quartile 1 (HR, 2.09; 95% CI: 0.90-4.84), Quartile 3 (HR, 2.44; 95% CI: 1.05-5.65) and Quartile 4 (HR, 3.38; 95% CI: 1.51-7.54) had poorer OS compared with Quartile 2. Similar results were found for BCSS and DFS. This study confirmed a U-shaped association between age at diagnosis and breast cancer outcome.

Examining the Impact of Cholecystectomy on Tumor Recurrence in Breast Cancer Patients.

Previous studies have found that bile acids influence the growth of breast cancer cells in vitro, suggesting that naturally occurring bile acids may also influence the growth of human breast cancer cells. Cholecystectomy alters modulation of bile acid metabolites, and therefore postcholecystectomy women could be at an increased risk of cancer development and recurrence. This study examined the breast cancer outcome in women who underwent cholecystectomy as compared to those with intact gallbladder. Ninety-three patients diagnosed with Stage I-III invasive mammary carcinoma in 2014 were retrospectively identified and patient demographics, treatment, and outcomes were collected and statistically analyzed. Results revealed 36% of patients who underwent cholecystectomy had recurrence compared to 25% recurrence in patients with intact gallbladders (p = .30). Forty-six percent of cholecystectomy patients were deceased, and 23% of those with intact gallbladder were deceased (p = .024). The effect of cholecystectomy on bile acid modulation and breast cancer recurrence requires further investigation.

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.

Association of statin use with clinical outcomes in patients with triple-negative breast cancer.

523 Background: Statins have been shown to target pathways related to breast cancer carcinogenesis, specifically in more aggressive breast cancer subtypes such as triple negative breast cancer (TNBC). Given the limited toxicity profile, low cost, and ease of use of statins, an association between statin therapy and improved breast cancer outcomes, particularly in aggressive breast cancers with more limited treatment options, could have important public health implications. Here we examine the association of statin therapy with breast cancer outcomes in women with stage I-III breast cancer, specifically TNBC. Methods: We utilized Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry (TCR)-Medicare data. We included women age 66 years or older with histologically confirmed stage I-III breast cancer diagnosed from 2008-2015. We used multivariable Cox proportional hazards regression models to examine the association of statin use with overall survival (OS) and breast cancer specific survival (BCSS) adjusting for age, race, education, state buy-in, residence area, stage, subtype, endocrine therapy, radiation, chemotherapy, surgery, baseline statin use, comorbidity, and baseline hypertension. For BCSS, we accounted for the competing risk of death using the Fine and Grey method. We required all individuals to survive until 12 months post-diagnosis, which we defined as the start of the follow-up period, to account for immortal time bias. Results: We identified 45,063 patients with stage I-III breast cancer meeting inclusion criteria, out of which 22,518 (50.0%) received a statin within one year following diagnosis (statin-users). The 5-year cumulative estimates of breast cancer specific deaths were 5.9% and 6.9% for statin-users and non-users (P <.001), respectively. In the overall cohort, adjusted models showed a statistically significant association between statin use and improved BCSS (subdistribution hazard ratio [SHR], 0.82; 95% CI, 0.70 to 0.97; P =.021), but no association with OS (hazard ratio [HR], 0.96; 95% CI, 0.90 to 1.03; P =.23). The association was strongest in patients with TNBC for BCSS (SHR, 0.60; 95% CI, 0.42 to 0.86; P =.006) and OS (HR, 0.76; 95% CI, 0.61 to 0.95; P =.018). Stratification by stage showed that the effect of statin therapy in TNBC was limited to patients with localized disease. Our results were consistent using propensity score matched models and when limiting our analysis to statin therapy initiated following breast cancer diagnosis. Conclusions: Among women with non-metastatic breast cancer, we found that statin use was associated with an OS and BCSS benefit among women with TNBC. Our data suggest that statins may have a role as an adjuvant therapy in select patients with breast cancer and supports further investigation, particularly among patients with TNBC, for whom effective treatment options are more limited.

Impact of African ancestry on the relationship between BMI and survival in early stage breast cancer: Retrospective analysis from E5103.

1010 Background: Both Black race and obesity are associated with worse survival in early stage breast cancer. Obesity disproportionately affects Black women; however, the degree this contributes to racial disparities in breast cancer remains unclear. Prior work evaluated heterogeneous populations or used self- reported race, rather than genetic ancestry. African ancestry is associated with higher BMI and worse survival in breast cancer; however, the intersection between genetic ancestry and obesity on survival outcomes remains unknown. Methods: We analyzed data from the adjuvant trial E5103. Patients with high risk, HER2 negative breast cancer received doxorubicin/cyclophosphamide x 4, followed by weekly paclitaxel x 12, with or without bevacizumab. Genetic ancestry was determined on the 2,854 patients with available germline DNA, BMI, and outcome data using principal components from a genome-wide array. The primary objective assessed impact of BMI on DFS and OS by ancestry. Multivariate Cox proportional hazard models evaluated correlation between continuous or binary BMI and survival in African (AA) and European (EA) Americans. Results: 13.4% of patients were genetically classified as AA and 86.6% as EA. Higher continuous BMI was significantly associated with worse DFS and OS only in AAs (DFS: HR = 1.25 95% CI 1.07-1.46, p = 0.004; OS: HR = 1.38 95% CI 1.10-1.73, p = 0.005); not in EAs (DFS HR = 0.97 95% CI 0.90-1.05, p = 0.50; OS HR = 1.03 95% CI 0.93-1.14, p = 0.52). By disease subtype, BMI was associated with worse outcomes only in AAs with ER+, and not TNBC. By categorical BMI, WHO class III obesity (³ 40) significantly associated with worse DFS and OS only in AAs (DFS HR = 1.98, p = 0.010; OS HR = 2.07, p = 0.064), not in EAs (DFS HR = 0.97, p = 0.86; OS HR = 1.28, p = 0.30). Proportion of African ancestry (proAA) was associated with higher BMI and worse outcomes in the total population; however, within AAs there was no significant interaction between proAA and BMI on DFS (HR = 0.36, p = 0.06) or OS (HR = 0.38, p = 0.24). In AAs, BMI remained associated with DFS (HR = 2.78, p = 0.019), suggesting higher BMI is associated with worse DFS regardless of proAA. Coefficients for the interaction term indicate that as proAA increases the impact of BMI on outcome is lessened. Conclusions: Higher BMI is significantly associated with worse breast cancer outcomes in women of African ancestry in E5103, but not in those of European ancestry. Categorically, this association was significant only for severe obesity, indicating the relationship may depend on the degree of obesity. As proAA increased in AAs, the impact of BMI on outcome was lessened, suggesting other host factors may contribute more to obesity’s influence on outcome than genetics. Determination of the optimal populations for weight loss interventions will advance precision medicine efforts to impact racial disparities and outcomes in early stage breast cancer.

Does HIV undermine breast cancer outcomes in women?

Does HIV undermine breast cancer outcomes in women?

10-Year Breast Cancer Outcomes in Women ≤35 Years of Age

Breast cancer diagnosis at a very young age has been independently correlated with worse outcomes. Appropriately intensifying treatment in these patients is warranted, even as we acknowledge the risks of potentially mutagenic adjuvant therapies. We examined local control, distant control, overall survival, and secondary malignancy rates by age cohort and by initial surgical strategy. Female patients less than or equal to 35 years of age diagnosed with invasive breast cancer from January 1, 1990, to December 31, 2010, were identified. Control groups of those aged 36 to 50 years (n = 6246) and 51 to 70 years (n = 7294) were delineated from an institutional registry. Clinicopathologic and follow-up information was collected. Chi-squared test was used to compare frequencies of categorical variables. Survival endpoints were evaluated using Kaplan-Meier methodology. A total of 529 patients ≤35 years of age met criteria for analysis. The median age of diagnosis was 32 years (range 20-35). Median follow-up was 10.3 years. On multivariable analysis, factors associated with overall survival (OS) were tumor size (hazard ratio [HR] 1.14, P = .02), presence of lymphovascular invasion (HR 2.2, P <.001), estrogen receptor positivity (HR 0.64, P = .015), receipt of adjuvant chemotherapy (HR 0.52, P = .035), and black race (HR 2.87, P <.001). The ultra-young were more likely to experience local failure compared with the aged 36 to 50 group (HR 2.2, 95% CI 1.8-2.6, P < .001) and aged 51 to 70 group (HR 3.1, 95% CI 2.45 - 3.9, P <.001). The cumulative incidence of secondary malignancies at 5 and 10 years was 2.2% and 4.4%, respectively. Receipt of radiation was not significantly associated with secondary malignancies or contralateral breast cancer. Survival and recurrence outcomes in breast cancer patients ≤35 years are worse compared with those aged 36 to 50 or 51 to 70 years. Based on our data, breast conservation therapy is appropriate for these patients, and the concern for second malignancies should not impinge on the known indications for postoperative radiation therapy.

Preserving fertility in young women undergoing chemotherapy for early breast cancer; the Maastricht experience

PurposeWe assessed the uptake of fertility preservation (FP), recovery of ovarian function (OFR) after chemotherapy, live birth after breast cancer, and breast cancer outcomes in women with early-stage breast cancer.MethodsWomen aged below 41 years and referred to our center for FP counseling between 2008 and 2015 were included. Data on patient and tumor characteristics, ovarian function, cryopreservation (embryo/oocyte) and transfer, live birth, and disease-free survival were collected. Kaplan–Meier analyses were performed for time-to-event analyses including competing risk analyses, and patients with versus without FP were compared using the logrank test.ResultsOf 118 counseled women with a median age of 31 years (range 19–40), 34 (29%) chose FP. Women who chose FP had less often children, more often a male partner and more often favorable tumor characteristics. The 5-year OFR rate was 92% for the total group of counseled patients. In total, 26 women gave birth. The 5-year live birth rate was 27% for the total group of counseled patients. Only three women applied for transfer of their cryopreserved embryo(s), in two combined with preimplantation genetic diagnosis (PGD) because of BRCA1-mutation carrier ship. The 5-year disease-free survival rate was 91% versus 88%, for patients with versus without FP (P = 0.42).ConclusionsRemarkably, most women achieved OFR, probably related to the young age at diagnosis. Most pregnancies occurred spontaneously, two of three women applied for embryo transfer because of the opportunity to apply for PGD.

Factors influencing breast cancer outcomes in Australia: A systematic review.

This systematic review evaluates factors influencing breast cancer outcomes for women treated in Australia, facilitating the exploration of disparities in breast cancer outcomes for certain groups of women in Australia. A systematic literature search was performed using MEDLINE and Scopus focusing on breast cancer in Australia with outcome measures being breast cancer survival and recurrence with no restrictions on date. Risk of bias was assessed using Cairns Assessment Scale for Observational studies of Risk factors (CASOR). Fifteen quantitative studies were included: two were high quality, 11 were intermediate quality, and two were low quality. Traditional risk factors such as invasive tumour type, larger size, higher grade and stage, lymph node involvement and absence of hormone receptors were found to be associated with breast cancer mortality. Being younger (<40years old) and older (>70years old), having more comorbidities, being of lower socioeconomic status, identifying as Aboriginal or Torres Strait Islander, living in more rural areas or having a mastectomy were factors found to be associated with poorer breast cancer outcomes. Despite the heterogeneity of the studies, this review identified significant risk factors for breast cancer mortality and recurrence. The use of this data would be most useful in developing evidence-based interventions and in optimising patient care through creation of a prediction model. CRD42017072857.

Non breast cancer outcomes in women who attend breast screening.

e13579Background: In Queensland, Australia, all women aged 50-74 are offered free breast screening. The plan evaluates non breast cancer outcomes for screened and non screened populations aged 50-6...

Influence of socioeconomic factors and distance to radiotherapy on breast-conserving surgery rates for early breast cancer in regional Australia; implications of change.

Breast conserving surgery rates are affected by many factors including distance to radiotherapy and tumor-related features. Numerous studies have found women who must travel further for radiotherapy are more likely to choose mastectomy and avoid radiotherapy. We examined relationships between socioeconomic group, distance to radiotherapy services and mastectomy rates across a range of rural and metropolitan settings. We used a dataset extracted from the Evaluation of Cancer Outcomes Barwon South Western Registry, which captured data on new breast cancer diagnoses in the southwest region of Victoria, Australia. Using logistic regression, we modeled treatment choice of women with early breast cancer (mastectomy vs breast conserving surgery) using explanatory variables that included distance to radiotherapy, and area-level socioeconomic data from the Australian Bureau of Statistics, while controlling for clinical factors. Mastectomy was associated with tumor size, nodal burden and younger age at surgery. Distance to a radiotherapy center was also strongly associated with increased rates of mastectomy for women who traveled 100-200km for radiotherapy (odds ratio=1.663; P=0.03) compared to the reference group who were within 100km of radiotherapy. No socioeconomic differences were seen between the two groups. A strong association between distance to radiotherapy and the type of surgery for early breast cancer was found. Improving access to radiotherapy therefore has the potential to improve breast cancer outcomes for women in regional Australia.

Abstract C27: Breast cancer presentation in a cohort of Afro-American women and Afro-Caribbean women diagnosed at University of Miami/Jackson Memorial Hospital

Abstract Background: It is documented that socioeconomic factors, such as lack of access to health care and inadequate treatment after diagnosis contribute to disparities in breast cancer, but these factors alone do not explain breast cancer disparities. Several studies suggest that several other factors, such as environmental, biological and behavioral factors may play a significant role in the observed disparities in breast cancer outcomes in women in minorities. In this study we compare Afro-Caribbean (AC) women born in the Caribbean and living in the United States and Afro-American (AA) women born and living in the United States, with a diagnosis of breast cancer in order to evaluate the effect of immigration and place of residency. Methods: We conducted a retrospective chart review study of black women of AA and AC origin diagnosed with breast cancer at University of Miami/Jackson Memorial Hospital between 2005 and 2015 (n = 745). For each of the groups, we collected demographic data including age, body mass index (BMI), menopausal state, and TNM stage, receptor expression of estrogen and progesterone, Her-2/neu expression, gravidity and parity. Continuous data were analyzed using independent samples t-tests when parametric and using Wilcoxon-Mann-Whitney tests when non-parametric; categorical and binary data were analyzed using Chi-squared tests. Results: We analyzed data from 745 black female patients: AA (n = 281) AC (n = 422). Place of birth was not available for 42 women. Mean age was 54.9 and 53.7 in AC and AA women, respectively. AA women had higher BMI (32.1 vs 29.8, p = 0.0001), lower proportion of HER2 positive breast cancer (12% vs 19%, p = 0.027) and more children (3.1 vs 2.8, p = 0.023) than AC. There was no difference in age (54.9 vs 53.7), premenopausal status (33% vs 31%), stage 3 or 4 (38% vs 37%), ER+ (63% vs 62%) or triple negative breast cancer (27% vs 31%) in AC compared with AA women (Table 1). Conclusion: Jackson Memorial Hospital is a Safety-Net hospital for the 2.4 million residents of Miami-Dade County. The average age of our cohort was 54 years, ER 63% positive, Stage 3 was 27% and triple negative breast cancer was 29%. Compared to SEER data, our patients developed breast cancer one decade earlier, had a higher rate of triple negative breast cancer and higher stage at presentation. This was not affected by immigration status although the AC women were thinner and had fewer children. Table 1.ACAAAAUSA(UM/JMH)(UM/JMH)(SEER)(SEER)Age55545863Age &amp;lt;50y29%35%25.7%18.3%Stage 3 or 438%37%19.3%12.8%ER+63%62%73%84%Her-2+19%12%19.7%16.1%Triple Negative27%31%11.9%5.5% Citation Format: Rochelle Marill, Keren Braithwaite, Jorge Monge, Diana Byrnes, Sophia George, Judith Hurley. Breast cancer presentation in a cohort of Afro-American women and Afro-Caribbean women diagnosed at University of Miami/Jackson Memorial Hospital. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C27.

Exercise and Prognosis on the Basis of Clinicopathologic and Molecular Features in Early-Stage Breast Cancer: The LACE and Pathways Studies.

To investigate whether the impact of postdiagnosis exercise on breast cancer outcomes in women diagnosed with early-stage breast cancer differs on the basis of tumor clinicopathologic and molecular features. Using a prospective design, 6,211 patients with early-stage breast cancer from two large population-based cohort studies were studied. Age-adjusted and multivariable Cox regression models were performed to determine the relationship between exercise exposure (total MET-hours/week) and recurrence and breast cancer-related death for: (i) all patients ("unselected" cohort), and on the basis of (ii) classic clinicopathologic features, (iii) clinical subtypes, (iv) PAM50-based molecular intrinsic subtypes, and (v) individual PAM50 target genes. After a median follow-up of 7.2 years, in the unselected cohort (n = 6,211) increasing exercise exposure was not associated with a reduction in the risk of recurrence (adjusted Ptrend = 0.60) or breast cancer-related death (adjusted Ptrend = 0.39). On the basis of clinicopathologic features, an exercise-associated reduction in breast cancer-related death was apparent for tumors <2 cm [HR, 0.50; 95% confidence interval (CI), 0.34-0.72], well/moderately differentiated tumors (HR, 0.63; 95% CI, 0.43-0.91), and ER-positive tumors (HR, 0.72; 95% CI, 0.53-0.97). Stratification by clinical subtype indicated that the ER(+)/PR(+)/HER2(-)/low-grade clinical subtype was preferentially responsive to exercise (recurrence: adjusted HR, 0.63; 95% CI, 0.45-0.88; breast cancer-related death: adjusted HR, 0.57; 95% CI, 0.37-0.86). The impact of exercise on cancer outcomes appears to differ as a function of pathologic and molecular features in early-stage breast cancer. Cancer Res; 76(18); 5415-22. ©2016 AACR.

The effect of metformin on breast cancer outcomes in patients with type 2 diabetes.

Observational data suggest that metformin use decreases breast cancer (BC) incidence in women with diabetes; the impact of metformin on BC outcomes in this population is less clear. The purpose of this analysis was to explore whether metformin use influences BC outcomes in women with type 2 diabetes. Prospective institutional databases were reviewed to identify patients with diabetes who received chemotherapy for stages I–III BC from 2000 to 2005. Patients diagnosed with diabetes before or within 6 months of BC diagnosis were included. Males and those with type I, gestational, or steroid-induced diabetes were excluded. Patients were stratified based on metformin use, at baseline, defined as use at time of BC diagnosis or at diabetes diagnosis if within 6 months of BC diagnosis. Kaplan–Meier methods were used to estimate rates of recurrence-free survival (RFS), overall survival (OS), and contralateral breast cancer (CBC). We identified 313 patients with diabetes who received chemotherapy for BC, 141 (45%) fulfilled inclusion criteria and 76 (54%) used metformin at baseline. There were no differences in clinical presentation or tumor characteristics between metformin users and nonusers. At a median follow-up of 87 months (range, 6.9–140.4 months), there was no difference in RFS (P = 0.61), OS (P = 0.462), or CBC (P = 0.156) based on metformin use. Five-year RFS was 90.4% (95% CI, 84–97) in metformin users and 85.4% (95% CI, 78–94) in nonusers. In this cohort of patients with type 2 diabetes receiving systemic chemotherapy for invasive BC, the use of metformin was not associated with improved outcomes.

Abstract P1-06-06: Alteration of stromal collagen fiber orientation in DCIS

Abstract Approximately 20% of new diagnoses of breast cancer are ductal carcinoma in situ (DCIS), a non-invasive form of breast cancer. Treatment decision-making for DCIS is challenging since current predictors of disease-free survival are limited, so that most women are presented with options for surgery, radiation and tamoxifen - all options with consequences for quality of life. Prior studies of prognostic factors for DCIS have focused on morphologic, genetic, and protein expression patterns of the DCIS cells. However, laboratory evidence suggests that the tumor microenvironment may play a key role in tumor invasion and progression. Collagen is the most abundant component of the stroma surrounding the breast ducts in which cancers develop. We previously observed that, in invasive breast cancer, tumors with greater numbers of collagen fibers aligned perpendicularly from the tumor were more likely to predict poor survival than tumors with collagen fibers in primarily parallel patterns near the tumor boundary (Conklin Am J Pathol 2011). To improve our ability to predict breast cancer outcomes in women with DCIS, we examined the alignment of collagen adjacent to ducts affected by DCIS to test whether alignment patterns were similar to patterns observed in tissue labeled as “normal” from biopsy and surgical sections. We evaluated collagen alignment in 255 Wisconsin women diagnosed with DCIS in 1997-2000 and followed for a median of 11.2 years (range 1-15). Stromal collagen alignment was evaluated from routine H&amp;E tissue slides prepared at the time of diagnosis using second harmonic generation (SHG) microscopy, a label-free multiphoton laser scanning technique that selectively images collagen. SHG images were acquired and evaluated for 3-5 regions on each DCIS and normal slide for each patient; the angles of collagen fibers with respect to the DCIS lesion/stroma boundary were calculated using customized imaging software. Data for the distribution of angles were compared for normal ducts and DCIS lesions using compositional data analysis with the number of fibers totaled according to 5-angle bins (1-5, 6-10, 11-15, …, 86-90 degrees). Repeated measures linear regression models were fit to log-transformed ratios of binned counts as a function of tissue type. Dependence among repeated counts within a single region was modeled using an unstructured variance-covariance matrix. Dependence among measurements within a single subject was modeled using a compound symmetry correlation structure. Overall, the distribution of collagen fiber angles from DCIS lesions differed significantly (P = 0.0002) from the distribution of collagen fibers surrounding normal ducts. Collagen fibers surrounding DCIS lesions were 11-18% more likely to orient at 75-90 degrees relative to the lesion boundary than fibers surrounding normal ducts; fibers were more similarly aligned in both DCIS lesions and normal ducts at other smaller angles. These results underscore the relevance of the tumor microenvironment, in particular the arrangement of the collagen fiber matrix. Planned data analysis will next examine whether collagen fiber alignment patterns differ between DCIS patients who did and did not experience a second breast cancer diagnosis over the course of follow-up. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-06-06.

Effect of Age on Breast Cancer Outcomes in Women With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From a Herceptin Adjuvant Trial

Previous research has suggested that young age at diagnosis is an independent risk factor for breast cancer recurrence and death. No prior studies have adequately controlled for human epidermal growth factor receptor 2 (HER2) status or anti-HER2 treatment. We sought to evaluate whether age was a prognostic or predictive factor in the HERA trial. We used 2-year median follow-up data and dichotomized age at 40 years to evaluate its prognostic effect on outcomes for women assigned to trastuzumab for 1 year or observation. Of the 1,703 women randomly assigned to 1 year of trastuzumab and 1,698 to observation, 722 (21%) were age ≤ 40 years at study entry. In separate Cox models, controlling for relevant prognostic and predictive factors, disease-free (DFS) and overall survival (OS) hazard ratios (HRs) were consistent for women age ≤ 40 versus > 40 years, regardless of treatment assignment (observation group: DFS HR age ≤ 40 v > 40 years, 1.18; 95% CI, 0.90 to 1.54; OS HR age ≤ 40 v > 40 years, 1.01; 95% CI, 0.60 to 1.69; trastuzumab group: DFS HR age ≤ 40 v > 40 years, 1.11; 95% CI, 0.81 to 1.51; OS HR age ≤ 40 v > 40 years, 1.18; 95% CI, 0.66 to 2.09). Interaction between age group and treatment effect was not statistically significant (DFS P = .89; OS P = .55). In a retrospective analysis of a large randomized controlled trial of women with early-stage HER2-positive breast cancer, age was not strongly associated with risk of early recurrence or prediction of benefit from trastuzumab therapy. Future research should investigate whether age is a predictor of later recurrence and evaluate the impact of age within groups with other tumor subtypes.

Tamoxifen Benefits and &lt;i&gt;CYP2D6&lt;/i&gt; Testing in Women With Hormone Receptor-Positive Breast Cancer

Cancer intervention strategies have been increasingly focused on developing therapies that are personalized and tailored to each individual's unique genetic profile. Evolving understanding of the metabolism and pharmacogenomics of tamoxifen, an early example of targeted therapy for women with hormone receptor-positive breast cancer, has created decision-making challenges for healthcare providers and their patients. This article reviews the pharmacology of tamoxifen, the genetics and physiology of the CYP2D6 enzyme system that has important effects on tamoxifen metabolism, and subset data analyses from large controlled, clinical trials that cast new light on previously held beliefs about the utility of CYP2D6 genotyping for predicting tamoxifen effectiveness and improved breast cancer outcomes in women with early-stage, hormone receptor-positive breast cancer.

Multivitamin use and breast cancer outcomes in women with early-stage breast cancer: the Life After Cancer Epidemiology study

Little is known about the relation of multivitamin use to breast cancer outcomes. 2,236 women diagnosed from 1997 to 2000 with early-stage breast cancer (Stage I ≥ 1 cm, II, or IIIA) were enrolled about 2 years post-diagnosis, primarily from the Kaiser Permanente Northern California Cancer Registry (83%). Multivitamin use pre-diagnosis and post-diagnosis was assessed via mailed questionnaire. Outcomes were ascertained yearly by self-report and verified by medical record review. Delayed-entry Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for sociodemographic, tumor, and lifestyle factors. Overall, 54 and 72% of the cohort reported using multivitamins pre- and post-diagnosis, respectively. A total of 380 recurrences, 212 breast cancer deaths, and 396 total deaths were confirmed. Compared to never use, multivitamin use after diagnosis was not associated with any outcome (recurrence HR = 0.92; 95% CI: 0.71, 1.20; total mortality HR = 0.92; 95% CI: 0.71, 1.19). Compared to never use, persistent use of multivitamins from pre- to post-diagnosis was associated with a non-significant decreased risk of recurrence (HR = 0.76; 95% CI: 0.54, 1.06) and total mortality (HR = 0.79; 95% CI: 0.56, 1.12). The protective associations were limited to women who had been treated by radiation only (P for trend = 0.048 and 0.083 for recurrence and total mortality, respectively) and both radiation and chemotherapy (P for trend = 0.015 and 0.095 for recurrence and total mortality, respectively). In stratified analyses, women who consistently used multivitamins before and after diagnosis and ate more fruits/vegetables (P for trend = 0.008) and were more physically active (P for trend = 0.034) had better overall survival. Multivitamin use along with practice of other health-promoting behaviors may be beneficial in improving breast cancer outcomes in select groups of survivors.

Abstract P4-09-12: The Effect of Age on Breast Cancer Outcomes in Women with Her-2 Positive Breast Cancer: Results from the HERA Trial

Abstract Background: Previous research has suggested that young age at diagnosis is an independent risk factor for breast cancer recurrence and death. However, young women are more likely to develop more aggressive subtypes of breast cancer and no prior studies have adequately controlled for Her-2/neu status or anti-Her-2 treatment. We sought to evaluate whether age is a prognostic factor in the HERA trial, which is a large randomized phase III trial of women with Her-2 positive early stage breast cancer who were randomized to receive trastuzumab (for one or two years) or observation following (neo)-adjuvant chemotherapy. Methods: We used 2 year median follow-up data from the HERA trial and conducted Cox proportional hazards models. Age was dichotomized at ≥40 years versus &amp;gt; 41 years to evaluate its prognostic effect on outcomes in women who received trastuzumab and those who did not. Only patients included in the 1-year trastuzumab and observation arms were included in the present analysis. Results: Of the 1703 women randomized to one-year of trastuzumab and 1698 to observation, 722 (21%) were age 40 or younger at study entry. Younger women were more likely to have node negative (33% vs 37%), estrogen receptor (ER)-negative (56 % vs 49%), and progesterone receptor (PR)-positive disease (41% vs 32%). In separate Cox models controlling for T and N stage, grade, ER and PR status, chemotherapy, endocrine therapy, and menopausal status at randomization, disease-free survival (DFS) hazard ratios were consistent for women ≥40 years compared with &amp;gt; 41 years old patients, regardless of whether they were assigned to observation or to receive trastuzumab. DFS were as follow: observation group: HR (younger/older) = 1.09, p-value = 0.62; trastuzumab group: HR (younger/older) = 1.05, p-value = 0.84. There was no statistically significant interaction between age and treatment (p=0.94). Conclusions: In women with early stage Her-2/neu positive breast cancer in a large RCT, age was not an independent predictor of risk of early recurrence. Future research to investigate whether age is a predictor of later risk of recurrence or is a predictor among women with other tumor subtypes is warranted. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-12.

Breast cancer survival in women of African descent living in the US and in the Caribbean: effect of place of birth

In order to shed light on genetic and environmental factors contributing to breast cancer health disparities, anonymous data from the cancer registry in Brooklyn, NY and two countries in the Caribbean, have been analyzed and compared. De-identified data were obtained on 3,710 women from three cancer registries in Brooklyn (New York), Guyana, and Trinidad, all having been diagnosed with breast cancer between 1995 and 2007, with follow-up through to early 2009. There was a significant difference in breast cancer survival according to race, place of birth, and place of residence. Women of African origin had a significantly worse survival than White women. Women born in the Caribbean had significantly worse survival in comparison to their counterpart born in the US, independently from their ethnic background (adjusted hazard ratio: 1.6; 95% CI: 1.2-2.1). A significant lower breast cancer survival was observed in African Caribbean women living in the Caribbean (HR: 1.8; 95% CI: 1.6-2.1) versus African-Caribbean women born in the Caribbean and living in the US (HR: 1.3; 95% CI 1.1-1.7), versus African-descent women born and living in the US. This study suggests that biological, behavioral, environmental, and clinical factors play a significant role in the observed difference in breast cancer outcome in women of Afro Caribbean descent.