Breast Cancer Index Research Articles

Abstract PD4-06: A clinical model for assessing the individual breast cancer risk in mammography screening

Abstract Background. Mammography screening reduces breast cancer mortality, but is suboptimal for the breast cancers that are not detected by the screening. These women are identified as symptomatic interval cancers with more aggressive tumors and worse pronosis. To efficiently screen for breast cancer the individual breast cancer risk should be determined. We describe a model that is suited for bi-annual screening programs and estimates the 2-year risk of breast cancer. The risk model could be used at most mammography screening units without adding substantial cost. Methods. The study was based on the population based prospective KARMA cohort including 70,877 participants. Mammograms were collected up to five years following baseline mammogram. A prediction model was developed using mammographic features (density, microcalcifications and masses), use of hormone replacement therapy (HRT), family history of breast cancer, menopausal status, and body mass index. Relative risks were calculated using conditional logistic regression and 2-year absolute risks were calculated Results. Comparing women at highest and lowest mammographic density yielded a 5-fold higher risk of breast cancer for women at highest density. When adding microcalcifications and masses to the model, high-risk women had a nearly 9-fold higher risk of breast cancer compared to those at lowest risk. In the full model, taking HRT use, family history of breast cancer and menopausal status into consideration, area under the curve (AUC) reached 0.73. We calculated the absolute 2-year risk of breast cancer based on national incidence and mortality rates. We also stratified women into risk groups using the NICE guidelines adapted to 2-year risks. The 20% women with moderate or high breast cancer risk were 7.6 times more likely to develop breast cancer compared to the general risk. Also 18% of the women showed 4 times reduced risk compared to the average population. Conclusions. This risk model can improve mammography screening by identifying women that are in need of additional examination procedures. There is also a substantial proportion of women with low breast cancer risk who will have little benefit from screening. Citation Format: Eriksson M, Czene K, Pawitan Y, Hall P. A clinical model for assessing the individual breast cancer risk in mammography screening [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD4-06.

Abstract ES5-2: Clinical and molecular profiles to identify who is at risk?

Abstract The persistent risk of recurrence from ER-positive primary breast cancer has been known for many years. It was recently described in detail and in relation to baseline clinicopathologic factors in a meta-analysis by the EBCTCG. This involved nearly 63,000 patients that had been prescribed 5 years of endocrine therapy and had reached the end of that time recurrence-free (Pan et al, NEJM, 2017, 377, 1836). Among other things this revealed that even among patients with T1N0 disease 13% had a distant recurrence between years 5 and 20. Our group have previously created a Clinical Treatment Score (CTS) from nodal status, tumor size, grade, age and type of adjuvant endocrine treatment and validated this for estimating risk of distant recurrence from the time of diagnosis. Drawing on a training dataset of 4,735 patients from the ATAC trial and a validation set of 6,711 patients from the BIG1-98 trial we created the CTS5, a prognostic score of risk from year 5, that features the same factors as CTS other than type of endocrine treatment (Dowsett et al, JCO, 2018, 36, 1941). Of note, only 4/304 patients with one to three positive nodes that were categorized as low risk in the validation set had a distant recurrence between years 5 and 10. The CTS5 calculator can be accessed online at www.cts5-calculator.com. There are several commercially available molecular profiles that estimate the risk of recurrence over years 0-10 after diagnosis in endocrine-treated primary breast cancer. In the TransATAC study some of these, including the EPClin and PAM50-ROR, show similar prognostic information over years 5-10 (after 5 years of endocrine therapy) as they do over years 0-5 (during endocrine therapy). In contrast, while the Oncotype Recurrence Score (RS) showed similar prognostic information to EPClin and PAM50-ROR in years 0-5 its performance in years 5-10 was substantially worse. Examination of the time-dependent prognostic relationship of each of the individual genes and modules in the RS showed that those patients with higher ER signaling had good prognosis before year 5 but poorer after year 5, suggesting that the cessation of endocrine therapy may lead to this poorer post-5 year outcome (Dowsett et al Clin Cancer Res, 2015, 21, 2763). A broad-based assessment of gene expression in the TransATAC sample set found that there was limited potential to identify a prognostic profile that performed substantially better after 5 years (Buus et al, Breast Cancer Res, 2018, 20, 103). One test, the 7-gene Breast Cancer Index, has reported on a relatively small sample set that it can predict the benefit or not from extended adjuvant endocrine therapy. Further validation studies of this are warranted as well as other tests that provide the same predictive information. Citation Format: Dowsett M. Clinical and molecular profiles to identify who is at risk? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES5-2.

Factors Impacting False Positive Recall in Screening Mammography

Our objective was to identify factors impacting false positive recalls in screening mammography. We retrospectively reviewed our screening mammography database from August 31, 2015 to September 30, 2016, including full field digital mammograms (FFDM) and digital breast tomosynthesis (DBT) mammograms. False positive (FP) exams were defined as Breast Imaging-Reporting and Data System (BI-RADS) 1 or 2 assessments at diagnostic imaging with 1 year cancer-free follow-up, Breast Imaging-Reporting and Data System 3 assessment at diagnostic imaging with 2 years cancer free follow-up, or biopsy with benign pathology. True positives were defined as malignant pathology on biopsy or surgical excision. We evaluated the association of FP recalls with multiple patient-level factors and imaging features. A total of 22,055 screening mammograms were performed, and 1887 patients were recalled (recall rate 8.6%). Recall rate was lower for DBT than full field digital mammograms (8.0% vs 10.6%, p < 0.001). FP results were lower if prior mammograms were available (90.8% vs 95.8%, p = 0.02), and if there was a previous benign breast biopsy (87.6% vs 92.9%, p = 0.01). Mean age for the FP group was lower than the true positive group (56.1 vs 62.9 years, p < 0.001). There were no significant differences in FP recalls based on history of high-risk lesions, family history of breast or ovarian cancer, hormone use, breast density, race, or body mass index. FP recalls were significantly less likely with DBT, in older women, in patients with prior mammograms available for comparison, and in patients with histories of benign breast biopsy. This study supports the importance of using DBT in the screening setting and obtaining prior mammograms for comparison.

Summary of head‐to‐head comparisons of patient risk classifications by the 21‐gene Recurrence Score® (RS) assay and other genomic assays for early breast cancer

Many genomic assays that assess recurrence risk in early breast cancer (EBC) are prognostic, but they differ in risk group stratification, which can affect clinical utility. Prospective outcomes of >60 K patients treated based on the 21-gene assay results have shown that chemotherapy may be safely omitted in EBC patents with low Recurrence Score (RS) results (RS < 18). Because of its extensive validation and wide clinical use, the RS assay is a common comparator in head-to-head studies with other assays. Published/presented studies of the RS assay performed on the same tumor samples with Breast Cancer Index (BCI), EndoPredict (EP) or EP+ clinical features (EPclin), MammaPrint (MMP) and/or Prosigna (ROR) assays were reviewed. Study findings were summarized descriptively.

Maximum standardized uptake value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography could replace pathological diagnosis in luminal breast cancer

Background: The maximum standardized uptake value (SUVmax) of 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is an essential tool for making a diagnosis and determining treatment response. This study aimed whether the SUVmax of 18 F-FDG PET/CT could replace pathological diagnosis in luminal type breast cancer. Methods: We retrospectively enrolled 85 patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (luminal-type) between August 2013 and January 2018 who underwent 18 F-FDG PET/CT scans before surgery and had not received any treatment before surgery at Fujisawa City Hospital. We evaluated the relationship between the SUVmax of 18 F-FDG PET/CT and the Ki-67 labeling index (LI) or other clinicopathological features in luminal-type breast cancer; furthermore, we evaluated whether the SUVmax of PET/CT can help determine whether adjuvant chemotherapy is indicated. Results: The SUVmax differed significantly between the positive and negative groups that showed lymphatic invasion (P=0.018), nuclear grade (P=0.019), and lymph node metastasis (P=0.035). In addition, a significant correlation was observed between the SUVmax and Ki-67 LI (r=0.516, P Conclusions: The SUVmax of 18 F-FDG PET/CT could replace pathological diagnosis in luminal breast cancer.

Ki-67 expression impact on lympho-vascular invasion presence in early breast cancer

Background/Aim:Lympho-vascular invasion (LVI) is associated with biologically aggressive cancers.The aim of this study was to investigate the correlation between LVI and immunohistochemical expression of the frequently routinely applied immuno-histochemical bio-marker Ki-67 proliferative index in early breast cancer .

The incidence and mortality of cancer in Eastern Mediterranean Regional Office (EMRO) and its relationship with Human Development Index (HDI): An Ecological Study

Background: the cancer was considered as the second cause of mortality in the developed countries and all around the world after the cardiovascular diseases. Also, it was reported as the third cause of mortality in the less developed countries after cardiovascular diseases. The current study was aimed to evaluate the epidemiology, incidence, and mortality of all cancers in East-Mediterranean region by gender and age.&#x0D; Methods: This study was an ecologic study in Asia for assessment of the correlation between age-specific incidence rate (ASIR) and age-specific mortality rate (ASMR) with HDI (life expectancy at birth, mean years of schooling and gross national income (GNI) per capita) Data about SIR and SMR for every Asian country for the year 2012 were obtained from the global cancer project. Correlation bivariate method for assessment of the correlation between incidence and mortality rates was used. Statistical analysis using Stata-14 and P 05/0, respectively and a significant &lt;0.05.&#x0D; Results: in East-Mediterranean region, some 555318 cases of cancer recorded in 2012. The highest incidence rates of cancer were reported for breast, colo-rectum, lung, liver, and bladder being 17.9%, 5.9%, 5.9%, 5.3%, and 5%, respectively. Also, the highest mortality of cancer were reported for breast, colo-rectum, lung, liver, and bladder being 11.5%, 5.8%, 5.9%, 7.6%, and 3.8%, respectively.&#x0D; The highest and lowest mortality ratios were reported for Somalia, and Saudi Arabia being 106.2, and 53.9 cases per 100000 people, respectively. Lung cancer and Human Development Index (HDI) had significant correlation with each other (P&gt; 0.05). Also, a significant correlation was seen between Human Development Index (HDI) and mortality rates of breast, colorectal, lung and liver cancer (P&gt; 0.05).&#x0D; Conclusion: the cancer was considered as one of the main causes of mortality in the most countries of East-Mediterranean region. The breast and colorectal cancers were reported as the most common types of cancer in this region. As for the alarming trend and remarkable distribution of cancer to the disease load in East-Mediterranean countries, controlling the cancer should be considered as one of the priorities of health policy.&#x0D; Key words: Cancer, Incidence, Mortality, Eastern Mediterranean Regional Office (EMRO).&#x0D;

The incidence and mortality of cancer in Eastern Mediterranean Regional Office (EMRO) and its relationship with Human Development Index (HDI): An Ecological Study

Background: the cancer was considered as the second cause of mortality in the developed countries and all around the world after the cardiovascular diseases. Also, it was reported as the third cause of mortality in the less developed countries after cardiovascular diseases. The current study was aimed to evaluate the epidemiology, incidence, and mortality of all cancers in East-Mediterranean region by gender and age.&#x0D; Methods: This study was an ecologic study in Asia for assessment of the correlation between age-specific incidence rate (ASIR) and age-specific mortality rate (ASMR) with HDI (life expectancy at birth, mean years of schooling and gross national income (GNI) per capita) Data about SIR and SMR for every Asian country for the year 2012 were obtained from the global cancer project. Correlation bivariate method for assessment of the correlation between incidence and mortality rates was used. Statistical analysis using Stata-14 and P 05/0, respectively and a significant &lt;0.05.&#x0D; Results: in East-Mediterranean region, some 555318 cases of cancer recorded in 2012. The highest incidence rates of cancer were reported for breast, colo-rectum, lung, liver, and bladder being 17.9%, 5.9%, 5.9%, 5.3%, and 5%, respectively. Also, the highest mortality of cancer were reported for breast, colo-rectum, lung, liver, and bladder being 11.5%, 5.8%, 5.9%, 7.6%, and 3.8%, respectively.&#x0D; The highest and lowest mortality ratios were reported for Somalia, and Saudi Arabia being 106.2, and 53.9 cases per 100000 people, respectively. Lung cancer and Human Development Index (HDI) had significant correlation with each other (P&gt; 0.05). Also, a significant correlation was seen between Human Development Index (HDI) and mortality rates of breast, colorectal, lung and liver cancer (P&gt; 0.05).&#x0D; Conclusion: the cancer was considered as one of the main causes of mortality in the most countries of East-Mediterranean region. The breast and colorectal cancers were reported as the most common types of cancer in this region. As for the alarming trend and remarkable distribution of cancer to the disease load in East-Mediterranean countries, controlling the cancer should be considered as one of the priorities of health policy.&#x0D; Key words: Cancer, Incidence, Mortality, Eastern Mediterranean Regional Office (EMRO).&#x0D;

Use of Multigene Prognostic Indices to Guide Clinical Decision-Making Regarding Adjuvant Systemic Therapy

Purpose of Review Several multigene assays have been developed to guide adjuvant therapy decisions for early-stage invasive breast cancer, including the 21-gene recurrence score, 70-gene assay, EndoPredict, PAM50 Risk of Recurrence, and Breast Cancer Index.

Age-specific breast cancer risk by body mass index and familial risk: prospective family study cohort (ProF-SC)

BackgroundThe association between body mass index (BMI) and risk of breast cancer depends on time of life, but it is unknown whether this association depends on a woman’s familial risk.MethodsWe conducted a prospective study of a cohort enriched for familial risk consisting of 16,035 women from 6701 families in the Breast Cancer Family Registry and the Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer followed for up to 20 years (mean 10.5 years). There were 896 incident breast cancers (mean age at diagnosis 55.7 years). We used Cox regression to model BMI risk associations as a function of menopausal status, age, and underlying familial risk based on pedigree data using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), all measured at baseline.ResultsThe strength and direction of the BMI risk association depended on baseline menopausal status (P < 0.001); after adjusting for menopausal status, the association did not depend on age at baseline (P = 0.6). In terms of absolute risk, the negative association with BMI for premenopausal women has a much smaller influence than the positive association with BMI for postmenopausal women. Women at higher familial risk have a much larger difference in absolute risk depending on their BMI than women at lower familial risk.ConclusionsThe greater a woman’s familial risk, the greater the influence of BMI on her absolute postmenopausal breast cancer risk. Given that age-adjusted BMI is correlated across adulthood, maintaining a healthy weight throughout adult life is particularly important for women with a family history of breast cancer.

Discrepancy in risk assessment of hormone receptor positive early-stage breast cancer patients using breast cancer index and recurrence score.

A recent comparison of the prognostic accuracy of Breast Cancer Index (BCI) and the Recurrence Score (RS) showed that BCI was more precise than RS. BCI identified a subset of RS low and intermediate risk patients with clinically relevant elevated rates of distant recurrences (DR). The current study analyzed the correlation of BCI and RS risk classification to clinical and pathological parameters and further examined the re-categorization between the two risk group indices in a multi-institutional cohort of hormone receptor positive (HR+) breast cancer patients. 560 women with HR+, lymph node-negative breast cancer who underwent testing with RS as part of their routine clinical care were included in the final analysis. Individual risk was assessed using predefined categories of RS and BCI (Low, Intermediate and High, respectively). Correlations between BCI, RS, and standard clinical-pathological prognostic factors were examined, and re-categorization of risk groups between BCI and RS was analyzed. An overall significant association between histological tumor grade and RS or BCI was observed with high-grade tumors more prevalent among RS and BCI high-risk patients. The invasive ductal carcinoma histologic subtype was associated with 98% and 93% of high-risk RS and BCI cases, respectively. The invasive lobular subtype accounted for 0% and 6% of high-risk RS and BCI cases, respectively. A poor agreement between the two biomarker risk group indices was demonstrated with more than 51% of the total cohort stratified differently between BCI and RS. As compared with RS, BCI stratified fewer patients into the intermediate-risk group (29% vs. 39%, BCI and RS, respectively) and more patients into the high-risk group (19% vs. 7%, BCI and RS, respectively). Subsets of both RS low- and intermediate-risk patients were identified by BCI as high risk. In this clinical series, BCI and RS risk groups demonstrated a significant association with histological tumor grade. BCI showed a modest correlation with tumor size and no correlation with age, while RS showed no correlation with tumor size or age. Compared with RS, BCI classifies fewer intermediate risk patients, identifies subsets of low and intermediate RS risk patients as high-risk, and provides distinct individualized risk assessment for patients with early-stage breast cancer.

Dietary inflammatory index and incidence of breast cancer in the SUN project

Breast cancer (BC) is the most commonly diagnosed cancer, and diet is suspected toplay a role in its development. Dietary factors may mediate this process through modulation of inflammation, though findings from previous studies have not been consistent. We aimed to longitudinally assess the association between the dietary inflammatory index (DII®), a frequently used method to assess the inflammatory potential of the diet, and incident BC. We included 10,713 middle-aged, Spanish female university graduates from the SUN cohort. DII® scores were derived from a validated 136-item food-frequency questionnaire, and it was based on scientific evidence on the relationship between diet and inflammatory biomarkers. Diagnosis of BC wasreported by the participant or, if deceased, by the next of kin or identified from death certificates. Self-reports of BC were confirmed by revision of medical reports by an experienced oncologist. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between quartiles of DII® and incident BC. After 10.3 years of median follow-up, we identified 100 confirmed and 168 probable incident BC cases. The multivariable-adjusted HR for participants in the 4th quartile to the 1st quartile was 1.44 (95% CI 0.76-2.72; p-trend: 0.339) when confirmed cases were analyzed, and 1.20 (95% CI 0.72-1.99; p-trend: 0.757) for the probable cases. We neither observed statistically significant differences in regard to menopausal status. The apparent increase in risk between DII® scores and BC in our cohort was not statistically significant, which could be partly explained by the small number of observed cases.

Dietary Inflammatory Index and Odds of Breast Cancer in a Case-Control Study from Iran

Chronic inflammation is implicated in breast cancer (BrCa) development; however, studies on the association of the inflammatory potential of diet and breast cancer have produced conflicting results. With this as background, we investigated the association between dietary inflammatory index (DII®) scores and BrCa risk in an Iranian case-control study. In this study, 136 newly diagnosed breast cancer patients and 272 hospitalized controls were recruited using convenience sampling. DII scores were computed from dietary intake data collected through a validated food frequency questionnaire (FFQ). Adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between the DII and BrCa risk were estimated by logistic regression. After controlling for multiple potential confounders, a significantly increased BrCa odds was observed in the highest quartile of DII score compared to the lowest quartile (ORquartile 4 vs. 1 = 2.64, 95% CI: 1.12–6.25; Ptrend = 0.01). In subanalysis based on menopausal status, a positive association was observed between the DII and BrCa risk among premenopausal women (ORquartile 4 vs. 1 = 5.51, 95% CI: 1.45–20.93; Ptrend = 0.005); however, no association was detected in postmenopausal women. Our findings suggest that more proinflammatory diets, indicated by higher DII scores, may increase the odds of BrCa, especially among premenopausal women.

Survival estimates stratified by the Nottingham Prognostic Index for early breast cancer: a systematic review and meta-analysis of observational studies

BackgroundEstimates of survival for women diagnosed with early staged breast cancer are available based on stratification into prognostic categories defined using the Nottingham Prognostic Index (NPI). This review aimed to identify and summarize the estimated survival statistics from separate sources in the literature and to explore the extent of between-study heterogeneity in survival estimates.MethodsObservational studies in women diagnosed with early and locally advanced breast cancer reporting overall survival by NPI category were identified using a systematic literature search. An exploratory meta-analysis was conducted to describe survival estimates and assess between-study heterogeneity.ResultsTwenty-eight studies were identified. Nineteen studies with sufficient data on overall survival were included in meta-analysis. A high level of heterogeneity in survival estimates was evident with I2 values in the range of 90 to 98%.ConclusionsThe substantial differences between studies in the relationship between NPI categories and survival at 5 and 10 years poses challenges for use of this prognostic score in both clinical settings and in decision-analytic model-based economic evaluations.

An Update on Breast Cancer Multigene Prognostic Tests—Emergent Clinical Biomarkers

Multigene signatures generate crucial prognostic information particularly useful for cancer patients where clinical parameters and traditional immunohistochemical markers alone lead to equivocal prognosis. Clinicians are now provided with molecular tools that assist in the outline of adjuvant therapies, namely helping decide on the extension of adjuvant endocrine therapy or on suppressing adjuvant chemotherapy in patients were toxic effects are particularly deleterious or when this treatment is fundamentally not needed. The importance of cancer multigene prognostic signatures is well elucidated in the guidelines for adjuvant systemic therapy in early-stage breast cancer and the guidelines on disease staging that are progressively integrating gene expression assays as classification biomarkers. In addition to the predictive and prognostic value, some genetic tests provide intrinsic subtyping classification. Herewith, we compare the molecular tests OncotypeDX, MammaPrint, Prosigna, EndoPredict, Breast Cancer Index, Mammostrat, and IHC4 and report the eligibility of each one in the suitable setting. Through to now, there is not a commercially available multigene test that makes recommendations regarding adjuvant treatment for HER-2 and triple negative breast cancers. Thus, these patients still receive adjuvant chemotherapy. Importantly, triple negative carcinomas are very heterogeneous regarding prognosis and new molecular signatures that decipher this very heterogeneous subgroup of breast cancer may improve the clinical management of the disease.

Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer

BackgroundSeveral prognostic signatures for early oestrogen receptor-positive (ER+) breast cancer have been established with a 10-year follow-up. We tested the hypothesis that signatures optimised for 0–5-year and 5–10-year follow-up separately are more prognostic than a single signature optimised for 10 years.MethodsGenes previously identified as prognostic or associated with endocrine resistance were tested in publicly available microarray data set using Cox regression of 747 ER+/HER2− samples from post-menopausal patients treated with 5 years of endocrine therapy. RNA expression of the selected genes was assayed in primary ER+/HER2− tumours from 948 post-menopausal patients treated with 5 years of anastrozole or tamoxifen in the TransATAC cohort. Prognostic signatures for 0–10, 0–5 and 5–10 years were derived using a penalised Cox regression (elastic net). Signature comparison was performed with likelihood ratio statistics. Validation was done by a case-control (POLAR) study in 422 samples derived from a cohort of 1449.ResultsNinety-three genes were selected by the modelling of microarray data; 63 of these were significantly prognostic in TransATAC, most similarly across each time period. Contrary to our hypothesis, the derived early and late signatures were not significantly more prognostic than the 18-gene 10-year signature. The 18-gene 10-year signature was internally validated in the TransATAC validation set, showing prognostic information similar to that of Oncotype DX Recurrence Score, PAM50 risk of recurrence score, Breast Cancer Index and IHC4 (score based on four IHC markers), as well as in the external POLAR case-control set.ConclusionsThe derived 10-year signature predicts risk of metastasis in patients with ER+/HER2− breast cancer similar to commercial signatures. The hypothesis that early and late prognostic signatures are significantly more informative than a single signature was rejected.

Non metastatic breast cancer and body mass index: High risk relation

Non metastatic breast cancer and body mass index: High risk relation

The expression and clinical significance of GADD45A in breast cancer patients.

BackgroundGrowth arrest and DNA-damage-inducible protein 45 alpha (GADD45A) was previously found to be associated with risk of several kinds of human tumors. Here, we studied the expression and clinical significance of GADD45A in breast cancer.MethodsWe performed an immunohistochemical study of GADD45A protein from 419 breast cancer tissues and 116 adjacent non-neoplastic tissues.ResultsSignificantly high GADD45A expression were observed in breast cancer tissues compared with adjacent non-neoplastic tissues (P < 0.001) and were independently correlative with estrogen receptor negative (P = 0.028) and high Ki-67 index (P < 0.001). Kaplan–Meier survival analysis revealed that patients with high GADD45A expression levels had a worse long-term prognosis in triple negative breast cancer (P = 0.041), but it was not an independent prognostic factor in multivariate analysis (P = 0.058).ConclusionsGADD45A expression levels are significantly correlative with estrogen receptor status and Ki-67 index in human breast cancer. Patients with triple negative breast cancer might be stratified into high risk and low risk groups based on the GADD45A expression levels.

Abstract B81: Changing fertility factors affecting breast cancer in the Bahamas

Abstract Introduction: There are many factors that affect breast and ovarian cancer incidence. Genetics, obesity, parity, age at menarche, age at first pregnancy, and family size are all determinants of breast and ovarian cancer risk and factors that differ between well-resourced countries and low- and middle-income countries (LMIC). These factors can be subject to rapid change. In addition, there are risks that are associated with the development of breast and ovarian cancer that are associated with race and ethnic group that are less well understood. The Caribbean is home to more than 20 million women, the majority of whom are of African ancestry. The demographics of the Caribbean basin in terms of finance, diet, and exposures are rapidly changing and these factors will, no doubt, be reflected in the rates of breast and ovarian cancer diagnosis. In this article, we propose to examine the changing factors that affect the development of breast and ovarian cancer in women with breast and ovarian cancer of Afro-Caribbean origin. Methods: This prospective study was approved by the University of Miami IRB and the Ministry of Health in the Bahamas. We recruited breast and ovarian cancer patients from public and private clinics in the Bahamas between September 2008 and January 2010. Women were eligible if they had been diagnosed with breast or ovarian cancer, and if at least one parent was born in the Bahamas. Data were analyzed from 250 women from 229 families. The cohort was divided into four groups depending on the year that they were born: &amp;lt;1950, 1950-1959, 1960-1969, or &amp;gt;1970. Data analysis was conducted using the c2 test or ANOVA with adjustment for clustered data. Results: Data analysis was conducted on the 250 patients, and the groups were broken down as follows: fifty-six patients were born before 1950, ninety-one were born between 1950-1959, seventy-one between 1960-1969, and thirty-two in or after 1970. The mean age of diagnosis of their first cancer decreased from 57 years (born before 1950) to 31 years (born in or after 1970, p&amp;lt;0.0001). Patients born before 1950 had more siblings (p=0.045), more pregnancies (p&amp;lt;0.0001), and more children (p&amp;lt;0.0001). They had their menarche at an older age (13.8 years vs to 12.7 years, p=0.028) and their first pregnancy at a younger age (21.6 years vs 24.8 years, p=0.021) when compared to the patients born in or after 1970. There was no difference in their body mass index or family history of breast and ovarian cancer. 3.6% of the women were diagnosed with ovarian cancer. At the time of enrollment to study, 21% of the cohort had a TAH-BSO. 59.4% of women born in the 1950s underwent a TAH-BSO. Multivariate analysis of women diagnosed with breast or ovarian cancer, born in the 1960s or 1970s, had a significant odds ratio of having a BRCA mutation, OR 2.88 (1.26, 6.57), p=0.012 and OR 4.06 (1.62, 10.36), p=0.003, respectively. Conclusions: The Bahamas has undergone a rapid change from a developing country fertility pattern in the 1950s and by 1970 to a developed country's fertility pattern, in one generation. These changes influence breast and ovarian cancer risk and are associated with younger age of onset of breast cancer. We documented that 2.8% of Bahamian women without breast or ovarian cancer who had a family history of breast cancer had a deleterious mutation in BRCA 1 or 2. 40% of the 1,857 unaffected women who were offered genetic testing had a family history; thus, the prevalence of these mutations in the population is approximately 1% overall. However, the incidence of ovarian cancer is low. The unintended consequence of TAH-BSO for birth control and menorrhagia is a decrease in expected rates of both breast cancer and ovarian cancer. Citation Format: Sophia HL George, Ana Sandoval Leon, Talia Donenberg, Raleigh Bulter, Darron Halliday, DuVaughn Curling, Theodore Turnquest, John Lunn, Mohammad R. Akbari, Steven Narod, Judith Hurley. Changing fertility factors affecting breast cancer in the Bahamas [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B81.

Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women

The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017. Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years. Invasive or in situ premenopausal breast cancer. Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor-positive and/or progesterone receptor-positive than for hormone receptor-negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor-positive and progesterone receptor-positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor-negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer overall. The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.