Prospective study of growth and development in older girls and risk of benign breast disease in young women

BACKGROUND:

In adult women with retrospective data, childhood adiposity, pubertal growth and development were associated with benign breast disease (BBD) and/or breast cancer. The authors prospectively evaluated these childhood/adolescent characteristics and BBD risk.

METHODS:

The Growing Up Today Study (GUTS) included females, aged 9‐15 years in 1996, who completed annual questionnaires through 2001, then 2003, 2005, and 2007. Participants annually/biennially provided information on menarche, height, and weight, from which the authors derived body mass index (BMI in kg/m²). Peak height growth velocity (PHV in cm/year) was estimated from longitudinal data. On 2005‐2007 surveys, 6899 females (18‐27 years of age) reported whether a healthcare provider ever diagnosed BBD (n = 147), and whether it was confirmed by biopsy (n = 67). Logistic models investigated risk factors adjusted for age, alcohol, pregnancy, and maternal history.

RESULTS:

More childhood adiposity (odds ratio [OR], 0.91/[kg/m²]; P = .04) and shorter adult height (OR, 0.93/inch shorter; P = .07) were associated with lower risk of biopsy‐confirmed BBD. Girls with most rapid height growth were at increased risk (OR, 2.12; P = .09) relative to those with the slowest growth. Age at menarche was not associated (OR, 1.11/year; P = .32) nor was adult BMI (adjusted for childhood BMI: OR, 1.01/[kg/m²]; P = .98); larger BMI increases (childhood to adulthood) were not protective (OR + 1.04/[kg/m²]; P = .37). Among girls with maternal breast cancer, those with more rapid growth had higher risk (OR, 1.47/[cm/year]; P = .02). All estimates were age‐adjusted.

CONCLUSIONS:

Increased BBD risk (likely evolving to elevated breast cancer risk) was observed in thinner girls, girls with the most rapid growth, and taller women. Contrary to expectations, later menarche age was not protective against BBD, consistent with studies that found BBD patients are not protected against breast cancer by later menarche. Cancer 2011. © 2011 American Cancer Society.     

Disparities in cancer screening in individuals with a family history of breast or colorectal cancer

BACKGROUND:

Understanding racial/ethnic disparities in cancer screening by family history risk could identify critical opportunities for patient and provider interventions tailored to specific racial/ethnic groups. The authors evaluated whether breast cancer (BC) and colorectal cancer (CRC) disparities varied by family history risk using a large, multiethnic population‐based survey.

METHODS:

By using the 2005 California Health Interview Survey, BC and CRC screening were evaluated separately with weighted multivariate regression analyses, and stratified by family history risk. Screening was defined for BC as mammogram within the past 2 years for women aged 40 to 64 years; for CRC, screening was defined as annual fecal occult blood test, sigmoidoscopy within the past 5 years, or colonoscopy within the past 10 years for adults aged 50 to 64 years.

RESULTS:

The authors found no significant BC screening disparities by race/ethnicity or income in the family history risk groups. Racial/ethnic disparities were more evident in CRC screening, and the Latino‐white gap widened among individuals with family history risk. Among adults with a family history for CRC, the magnitude of the Latino‐white difference in CRC screening (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11‐0.60) was more substantial than that for individuals with no family history (OR, 0.74; 95% CI, 0.59‐0.92).

CONCLUSIONS:

Knowledge of their family history widened the Latino‐white gap in CRC screening among adults. More aggressive interventions that enhance the communication between Latinos and their physicians about family history and cancer risk could reduce the substantial Latino‐white screening disparity in Latinos most susceptible to CRC. Cancer 2011;. © 2011 American Cancer Society.     

Lobule type and subsequent breast cancer risk: Results from the Nurses' Health Studies

BACKGROUND:

Lobules in normal breast tissue can be classified based on their degree of development, which may affect their susceptibility to carcinogenesis. However, few epidemiologic studies to date have addressed this.

METHODS:

The authors examined the association between lobule type and subsequent breast cancer risk in a nested case‐control study of benign breast disease (BBD) and breast cancer within the Nurses' Health Studies (200 cases, 915 controls). Benign breast biopsy slides were reviewed by pathologists, and normal terminal duct lobular units were classified as having no type 1 lobules, mixed lobule types, or predominant type 1 and no type 3 lobules. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the association between lobule type and breast cancer risk.

RESULTS:

Women with predominant type 1 and no type 3 lobules (54 cases, 321 controls) had a decreased risk of breast cancer compared with those with no type 1 lobules or mixed lobule types (OR=0.63; 95% CI, 0.44‐0.91), although this was attenuated after adjustment for histologic category of BBD (OR=0.71; 95% CI, 0.49‐1.02). Having predominant type 1 lobules and no type 3 lobules was associated with a similar risk reduction for all categories of BBD (nonproliferative: OR=0.73 [95% CI, 0.36‐1.50]; proliferative without atypia: OR=0.80 [95% CI, 0.47‐1.35]; and atypical hyperplasia: OR=0.61 [95% CI, 0.28‐1.35]).

CONCLUSIONS:

These results provided preliminary evidence that lobule type may be an important marker of breast cancer risk in women with BBD. Cancer 2009. © 2009 American Cancer Society.     

SNP-SNP interactions between DNA repair genes were associated with breast cancer risk in a Korean population

BACKGROUND:

Single nucleotide polymorphisms (SNPs) in nucleotide excision repair (NER) pathway genes may modulate DNA repair capacity and increase susceptibility to breast cancer (BC). A case‐control study was conducted by evaluating genes involved in DNA repair to identify polymorphisms associated with BC.

METHODS:

The 384 SNPs of 38 candidate genes were genotyped using the Illumina GoldenGate method. Genotypes were determined in a case‐control study that consisted of 346 BC patients and 361 controls. Odds ratios and 95% confidence intervals were computed using logistic regression models. Multiple logistic regression models adjusted for age, family history of BC, and body mass index were used.

RESULTS:

Gene–gene interaction analysis among the DNA repair pathway genes showed significant effects on BC risk. ERCC2 rs50872 (TC genotype) in combination with XPA rs2808668 (TC genotype) and rs1800975 (AG genotype) was strongly associated with an increased risk of BC (P = .0004 and .0002, P_Bonferroni = .023 and .014, respectively). Moreover, the T‐G (including rs2808668 and rs1800975) haplotype in XPA combined with the ERCC2 T allele in rs50872 carriers was also associated with additive risk effect of BC (odds ratios: 2.58, 2.62, and 3.49, respectively).

CONCLUSION:

Genetic variation in DNA repair genes involved in NER mechanisms increased the risk of BC development. These results suggested that a stronger combined effect of SNPs via gene–gene interaction may help to predict BC risk. Cancer 2012;. © 2011 American Cancer Society.     

First international consensus conference on standardization of oncoplastic breast conserving surgery

Purpose

Body size, from birth throughout adulthood, is associated with breast cancer risk, but few studies have investigated early-life body size and benign breast disease (BBD), a well-established breast cancer risk factor. We consider whether prenatal factors and size at birth, 10, 18 year, and intervening growth, are related to BBD risk.

Methods

The Growing Up Today Study includes 9032 females who completed questionnaires annually from 1996 to 2001, then 2003, 2005, 2007, 2010, and 2013. In 1996, their mothers provided pregnancy-related data. From 2005 to 2013, participants (18 year+) reported whether they had ever been diagnosed with biopsy-confirmed BBD (N = 142 cases).

Results

Girls had greater adiposity (BMI; kg/m²) at 10 year if they were larger at birth, if mother’s pre-pregnancy BMI was higher, or if gestational weight gain was greater (all p < .01). Maternal height was (positively) associated (p < .05) with adolescent peak height growth velocity (PHV; in./year). Greater 10 year adiposity was associated with lower PHV and less height growth 10–18 year (both p < .01). Adiposity at 10 year was inversely associated with BBD (OR 0.83/(kg/m²), p < .01) as was increasing adiposity 10–18 year (OR 0.85/(kg/m²), p = .01). In a separate model, 10 year height (OR 1.13/in., p = .02) and height growth 10–18 year (OR 1.19/in.; p < .01) were positively associated. PHV was similarly positively associated (OR 2.58, p = .01, fastest versus slowest growth quartiles). In a multivariable model of BBD risk, gestational weight gain (daughters at highest risk if <20 lb gained), PHV (slowest growing girls at lowest risk), age 10 year height (positive), and BMI (inverse) were the most critical childhood risk factors (each p < .05).

Conclusions

Body size factors from pregnancy through adolescence were independently associated with BBD risk in young women.

     

The risk of primary and contralateral breast cancer after ovarian cancer in BRCA1/BRCA2 mutation carriers

BACKGROUND:

The objective of this study was to assess the incidence of primary breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had BRCA1/BRCA2‐associated epithelial ovarian cancer (OC).

METHODS:

From the database of the Rotterdam Family Cancer Clinic, patients who had BRCA‐associated OC without a history of unilateral breast cancer (BC) (at risk of PBC; n = 79) or with a history of unilateral BC (at risk of CBC; n = 37) were selected. The control groups consisted of unaffected BRCA mutation carriers (n = 351) or mutation carriers who had a previous unilateral BC (n = 294), respectively. The risks of PBC and CBC were calculated using the Kaplan‐Meier survival method with death considered as a competing risk event.

RESULTS:

Women with BRCA‐associated OC had lower 2‐year, 5‐year, and 10‐year risks of PBC (3%, 6%, and 11%, respectively) compared with unaffected mutation carriers (6%, 16%, and 28%, respectively; P = .03), although they had a considerably higher mortality rate at similar time points (13%, 33%, and 61%, respectively, vs 1%, 2%, and 2%, respectively; P < .001). In BRCA mutation carriers with a previous unilateral BC, the 2‐year, 5‐year, and 10‐year risks of CBC were nonsignificantly lower in patients with OC than in those without OC (0%, 7%, and 7%, respectively, vs 6%, 16%, and 34%, respectively; P = .06), whereas the mortality rate was higher in patients with OC (19%, 34%, and 55%, respectively, vs 4%, 11%, and 21%, respectively; P < .001).

CONCLUSIONS:

Patients with BRCA‐associated OC had a lower risk of developing a subsequent PBC or CBC than mutation carriers without OC, whereas the risk of dying from OC was greater than the risk of developing BC. These data may facilitate more tailored counseling for this patient subgroup, although confirmative studies are warranted. Cancer 2013. © 2012 American Cancer Society.     

Evaluation of a breast cancer risk prediction model expanded to include category of prior benign breast disease lesion

BACKGROUND:

Benign breast diseases (BBD) encompass several histologic subtypes with various risks of subsequent breast cancer. Information on previous benign breast disease biopsies has been incorporated into breast cancer risk prediction models; however, the type of histologic lesion has not been taken into account. Given the substantial heterogeneity in breast cancer risk dependent on the type of benign lesion, the authors evaluated whether incorporating this level of detail would improve the discriminatory power of risk classification models.

METHODS:

By using data from the Nurses' Health Study, a breast cancer nested case‐control study (240 cases; 1036 controls), the authors determined predictors of categories of BBD lesions and developed imputation models. The type of BBD, imputed for each cohort member who reported a diagnosis, was added to a modified version of the Rosner‐Colditz breast cancer risk prediction model.

RESULTS:

Compared with the model that included only previous BBD (yes/no), the model that included categories of BBD was significantly improved (P < .0001). Overall, including the category of BBD increased the concordance statistic from 0.628 to 0.635. By using risk reclassification, inclusion of the type of BBD resulted in a 17% increase in incidence per increase of 1 risk decile, holding the model without BBD type risk decile constant.

CONCLUSIONS:

Although the current data suggested that the inclusion of BBD category may improve breast cancer risk classification, the clinical utility of such a model will depend on the consistency of histologic classification of benign breast disease lesions. Cancer 2010. © 2010 American Cancer Society.     

Benign breast disease increases breast cancer risk independent of underlying familial risk profile: Findings from a Prospective Family Study Cohort

Benign breast disease (BBD) is an established breast cancer (BC) risk factor, but it is unclear whether the magnitude of the association applies to women at familial or genetic risk. This information is needed to improve BC risk assessment in clinical settings. Using the Prospective Family Study Cohort, we used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of BBD with BC risk. We also examined whether the association with BBD differed by underlying familial risk profile (FRP), calculated using absolute risk estimates from the Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model. During 176,756 person-years of follow-up (median: 10.9 years, maximum: 23.7) of 17,154 women unaffected with BC at baseline, we observed 968 incident cases of BC. A total of 4,704 (27%) women reported a history of BBD diagnosis at baseline. A history of BBD was associated with a greater risk of BC: HR = 1.31 (95% CI: 1.14–1.50), and did not differ by underlying FRP, with HRs of 1.35 (95% CI: 1.11–1.65), 1.26 (95% CI: 1.00–1.60), and 1.40 (95% CI: 1.01–1.93), for categories of full-lifetime BOADICEA score <20%, 20 to <35%, ≥35%, respectively. There was no difference in the association for women with BRCA1 mutations (HR: 1.64; 95% CI: 1.04–2.58), women with BRCA2 mutations (HR: 1.34; 95% CI: 0.78–2.3) or for women without a known BRCA1 or BRCA2 mutation (HR: 1.31; 95% CI: 1.13–1.53) (p_interaction = 0.95). Women with a history of BBD have an increased risk of BC that is independent of, and multiplies, their underlying familial and genetic risk.     

Prognostic value of positive human epidermal growth factor receptor 2 status and negative hormone status in patients with T1a/T1b, lymph node-negative breast cancer

BACKGROUND:

The objective of this study was to evaluate prognostic factors of local and distant recurrence in patients diagnosed with T1a and T1b, lymph node‐negative breast carcinoma (BC) with emphasis on human epidermal growth factor receptor 2 (HER2) status.

METHODS:

The authors reviewed 704 women with T1aT1bN0M0 BC who received treatment at the Radiation‐Oncology Center of Florence University between November 2002 and December 2008. Patients with ductal carcinoma in situ or recurrent BC at presentation and patients who received adjuvant chemotherapy were excluded from the analysis.

RESULTS:

In total, 75 patients had HER2‐positive BC (10.7%). At a mean follow‐up of 4.9 years (standard deviation, 2.6 years; range, 0.5‐10.8 years), 19 events were identified, including 10 distant recurrences. Patients with HER2‐positive BC had worse distant recurrence‐free survival (DRFS) than patients with HER2‐negative BC (hazard ratio, 3.66; 95% confidence interval, 0.94‐14.69; P = .045). Negative hormone receptor (HR) status was associated significantly with worse DRFS (hazard ratio, 0.26; 95% confidence interval, 0.07‐0.93; P = .026). In multivariate analysis, younger age was the only significant risk factor for an event of recurrence (hazard ratio, 0.61;95% confidence interval, 0.20‐1.82; P = .029).

CONCLUSIONS:

The current results indicated that patients with T1a/T1b, lymph node‐negative BC have a low risk of distant and local recurrence, but younger age is a significant risk factor for events occurrence. Young women with HER2‐positive and HR‐negative status have a significant risk of distant recurrence and should be considered for future clinical trials with anti‐HER2 adjuvant therapy. Cancer 2011. © 2011 American Cancer Society.     

Breast reconstructive surgery in medically underserved women with breast cancer

BACKGROUND:

Breast reconstructive surgery can improve mastectomy patients' emotional relationships and social functioning, but it may be underutilized in low‐income, medically underserved women. This study assessed the impact of patient‐physician communication on rates of breast reconstructive surgery in low‐income breast cancer (BC) women receiving mastectomy.

METHODS:

A cross‐sectional, California statewide survey was conducted of women with income less than 200% of the Federal Poverty Level and receiving BC treatment through the Medicaid Breast and Cervical Cancer Treatment Program. A subset of 327 women with nonmetastatic disease who underwent mastectomy was identified. Logistic regression was used for data analysis. The chief dependent variable was receipt of or planned breast reconstructive surgery by patient report at 6 months after diagnosis; chief independent variables were physician interactive information giving and patient perceived self‐efficacy in interacting with physicians.

RESULTS:

Greater physician information giving about BC and its treatment and greater patient perceived self‐efficacy positively predicted breast reconstructive surgery (OR = 1.12, P = .04; OR = 1.03, P = .01, respectively). The observed negative effects of language barriers and less acculturation among Latinas and lower education at the bivariate level were mitigated in multivariate modeling with the addition of the patient‐physician communication and self‐efficacy variables.

CONCLUSIONS:

Empowering aspects of patient‐physician communication and self‐efficacy may overcome the negative effects of language barriers and less acculturation for Latinas, as well as of lower education generally, on receipt of or planned breast reconstructive surgery among low‐income women with BC. Intervening with these aspects of communication could result in breast reconstructive surgery rates more consistent with the general population and in improved quality of life among this disadvantaged group. Cancer 2009. © 2009 American Cancer Society.     

Prevalence of BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and pancreatic cancer

BACKGROUND:

Germline mutations in the BRCA2 cancer susceptibility gene are associated with an increased risk of pancreatic cancer (PC). Breast‐pancreas cancer families with BRCA1 mutations have also been observed. The influence of a family history (FH) of PC on BRCA mutation prevalence in patients with breast cancer (BC) is unknown.

METHODS:

A clinical database review (2000‐2009) identified 211 Ashkenazi Jewish (AJ) BC probands who 1) underwent BRCA1/2 mutation analysis by full gene sequencing or directed testing for Ashkenazi founder mutations (BRCA1: 185delAG and 5382insC; BRCA2: 6174delT) and 2) had a FH of PC in a first‐, second‐, or third‐degree relative. For each proband, the pretest probability of identifying a BRCA1/2 mutation was estimated using the Myriad II model. The observed‐to‐expected (O:E) mutation prevalence was calculated for the entire group.

RESULTS:

Of the 211 AJ BC probands with a FH of PC, 30 (14.2%) harbored a BRCA mutation. Fourteen (47%) of the mutations were in BRCA1 and 16 (53%) were in BRCA2. Patients diagnosed with BC at age ≤ 50 years were found to have a higher BRCA1/2 mutation prevalence than probands with BC who were diagnosed at age > 50 years (21.1% vs 6.9%; P = .003). In patients with a first‐, second‐, or third‐degree relative with PC, mutation prevalences were 15.4%, 15.3%, and 8.6%, respectively (P = .58). In the overall group, the observed BRCA1/2 mutation prevalence was 14.2% versus an expected prevalence of 11.8% (O:E ratio, 1.21; P = .15).

CONCLUSIONS:

BRCA1 and BRCA2 mutations are observed with nearly equal distribution in AJ breast‐pancreas cancer families, suggesting that both genes are associated with PC risk. In this population, a FH of PC was found to have a limited effect on mutation prevalence. Cancer 2011;. © 2011 American Cancer Society.     

The prognostic contribution of clinical breast cancer subtype, age, and race among patients with breast cancer brain metastases

BACKGROUND:

Brain metastases (BM) arising from triple‐negative breast cancer (TNBC) portend a poor prognosis. TNBC is more common in premenopausal and African‐American (AA) patients; both of these characteristics also confer a poor prognosis. In a single‐institution cohort study, the authors attempted to determine whether the inferior outcome noted with TNBC brain metastases is more reflective of a higher risk population or the subtype itself.

METHODS:

The University of North Carolina Breast Cancer Database identified patients with BC brain metastases who were diagnosed between 1988 and 2008. BC subtype was assigned by immunohistochemistry: hormone receptor (HR) positive (+);(HR, estrogen receptor [ER]+ and/or progesterone receptor [PR]+)/human epidermal growth factor receptor 2 (HER2) negative (‐), HR+/HER2+, HR‐/HER2+, and TN (ER‐/PR‐/HER2‐). Survival and disease recurrence patterns were evaluated by subtype, patient age (<40 years vs ≥40 years), and race (AA vs non‐AA) using the Kaplan‐Meier method and Cox regression analysis.

RESULTS:

Among 119 patients with BC brain metastases, 33% were AA and 31% were aged <40 years. BC subtype was confirmed in 98 patients (30% with HR+/HER2‐, 21% with HR+/HER2+, 18% with HR‐/HER2+, and 31% with TNBC). Survival after BM was found to be impacted by subtype (P = .002), and was shortest for patients with TNBC (0.24 years; 95% confidence interval, 0.17 years‐0.48 years). There were no age‐specific (P = .84) or race‐specific (P = .09) differences in survival noted after brain metastases; stratification of BC subtypes by age and race revealed no difference (all, P > .1). The receipt of systemic therapy after BC brain metastases was found to be an important predictor of survival after BC brain metastases (hazard ratio, 0.29; P = .002) when adjusted for race, age, number of central nervous system lesions, and BC subtype.

CONCLUSIONS:

TNBC confers a high risk of death after brain metastases regardless of patient race and age, supporting the need for novel agents capable of controlling both intracranial and extracranial TNBC across all races and ages. Cancer 2011. © 2010 American Cancer Society.     

Prevalence of BRCA mutations in an unselected population of triple-negative breast cancer

BACKGROUND:

This study assessed BRCA1 and BRCA2 mutation prevalence in an unselected cohort of patients with triple‐negative breast cancer (BC).

METHODS:

One hundred ninety‐nine patients were enrolled. Triple negativity was defined as <1% estrogen and progesterone staining by immunohistochemistry and HER‐2/neu not overexpressed by fluorescence in situ hybridization. Having given consent, patients had BRCA1 and BRCA2 full sequencing and large rearrangement analysis. Mutation prevalence was assessed among the triple‐negative BC patients and the subset of patients without a family history of breast/ovarian cancer. Independent pathological review was completed on 50 patients.

RESULTS:

Twenty‐one deleterious BRCA mutations were identified—13 in BRCA1 and 8 in BRCA2 (prevalence, 10.6%). In 153 patients (76.9%) without significant family history (first‐degree or second‐degree relatives with BC aged <50 years or ovarian cancer at any age), 8 (5.2%) mutations were found. By using prior National Comprehensive Cancer Network (NCCN) guidelines recommending testing for triple‐negative BC patients aged <45 years, 4 of 21 mutations (19%) would have been missed. Two of 21 mutations (10%) would have been missed using updated NCCN guidelines recommending testing for triple‐negative BC patients aged <60 years.

CONCLUSIONS:

The observed mutation rate was significantly higher (P = .0005) than expected based on previously established prevalence tables among patients unselected for pathology. BRCA1 mutation prevalence was lower, and BRCA2 mutation prevalence was higher, than previously described. Additional mutation carriers would have met new NCCN testing guidelines, underscoring the value of the updated criteria. Study data suggest that by increasing the age limit to 65 years, all carriers would have been identified. Cancer 2011;. © 2011 American Cancer Society.     

Late age at first full term birth is strongly associated with lobular breast cancer

BACKGROUND:

Late age at first full‐term birth and nulliparity are known to increase breast cancer risk. The frequency of these risk factors has increased in recent decades.

METHODS:

The purpose of this population‐based case‐control study was to examine associations between parity, age at first birth (AFB), and specific histological subtypes of breast cancer. Women with breast cancer were identified from cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control subjects were randomly selected from population lists. Interviews collected information on reproductive histories and other risk factors. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of ductal, lobular, and mixed ductal‐lobular breast cancer diagnosis in association with AFB and nulliparity.

RESULTS:

AFB ≥30 years was associated with a 2.4‐fold increase in risk of lobular breast cancer compared with AFB <20 years (OR, 2.4; 95% CI, 1.9‐2.9). The association was less pronounced for ductal breast cancer (OR, 1.3; 95% CI, 1.2‐1.4). Nulliparity was associated with increased risk for all breast cancer subtypes, compared with women with AFB <20 years, but the association was stronger for lobular (OR, 1.7; 95% CI, 1.3‐2.2) than for ductal (OR, 1.2; 95% CI, 1.1‐1.3) subtypes (P = .004). The adverse effects of later AFB was stronger with obesity (P = .03) in lobular, but not ductal, breast cancer.

CONCLUSIONS:

Stronger associations observed for late AFB and nulliparity suggest that these factors preferentially stimulate growth of lobular breast carcinomas. Recent temporal changes in reproductive patterns and rates of obesity may impact the histological presentation of breast cancer. Cancer 2011. © 2010 American Cancer Society.     

Risk of metachronous breast cancer after BRCA mutation–associated ovarian cancer

BACKGROUND:

This study sought to estimate the risk of breast cancer (BC) after a diagnosis of ovarian cancer (OC) associated with mutation of the BRCA1/2 (breast cancer, early onset) genes (BRCA‐OC).

METHODS:

The Memorial Sloan‐Kettering Cancer Center and the University of Pennsylvania, clinical genetics databases were searched to identify women with BRCA‐OC who participated in genetic testing and follow‐up studies from 1995 to 2009. The primary objective was to determine the risk of developing BC after BRCA‐OC. Overall survival (OS) and BC‐free survival (BCFS) were determined by the Kaplan‐Meier method; patients were censored at the time of last follow‐up.

RESULTS:

A total of 164 patients had BRCA‐OC (115 with BRCA1; 49 with BRCA2). Of these 164 patients, 152 developed OC prior to BRCA testing (median time to testing, 2.4 years [0.01‐55 years]). Median follow‐up from OC for those not developing BC was 5.8 years (0.25‐55.6 years). There were 46 deaths, but none were due to BC. The 5‐ and 10‐year OS were 85% (95% confidence interval [CI] = 0.78, 0.90) and 68% (95% CI = 0.59, 0.76), respectively. There were 18 metachronous BC diagnoses. The 5‐ and 10‐year BCFS were 97% (95% CI = 0.92, 0.99) and 91% (95% CI = 0.82, 0.95), respectively. A subset of 64 women were tested either before or within 12 months of BRCA‐OC. In this pseudo‐incident subset, 5‐ and 10‐ year OS was 71% (95% CI = 0.53, 0.83) and 62% (95% CI = 0.44, 0.75), respectively, and 5‐ and 10‐year BCFS were 100% and 87% (95% CI = 0.56, 0.96), respectively.

CONCLUSIONS:

OS was dominated by OC deaths. Metachronous BC risk was lower than reported for unaffected BRCA mutation carriers. These results support nonsurgical management of BC risk in women with BRCA‐OC. Cancer 2013. © 2012 American Cancer Society.     

The impact of having a sister diagnosed with breast cancer on cancer‐related distress and breast cancer risk perception

BACKGROUND:

A family history of breast cancer has been shown to affect psychosocial functioning. However, the majority of research has focused on the daughters of patients with breast cancer and families with multiple relatives with the disease. The purpose of the current study was to examine cancer‐related distress and breast cancer risk perception, and further examine the predictors of these outcomes, in the sisters of newly diagnosed patients with breast cancer without a previous family history of the disease.

METHODS:

Sisters of newly diagnosed index breast cancer patients were identified and asked to complete a study‐specific questionnaire (demographics and cancer risk perception) and the Impact of Events Scale. Pathological information was abstracted from the medical chart for the index breast cancer patients.

RESULTS:

A total of 205 sisters completed the questionnaires. The mean time between breast cancer diagnosis and the sisters' completion of the questionnaire was 9.8 months. Approximately one‐half of the women scored in the moderate or severe distress range. The most significant predictor of cancer‐related distress was perceived lifetime breast cancer risk (P = .04). Women with a lifetime risk of breast cancer > 20% were more than twice as likely to have moderate or severe distress compared with those with a lifetime risk of < 20%.

CONCLUSIONS:

Cancer‐related distress is high in the sisters of newly diagnosed patients with breast cancer in whom there is no other family history of breast cancer. Specifically, women with a perceived lifetime risk of breast cancer of > 20% experienced the highest levels of distress. Future interventions that target this group should be considered. Cancer 2013. © 2013 American Cancer Society.     

Medical radiation,family history of cancer,and benign breast disease in relation to breast cancer risk in young women,USA

OBJECTIVE: In previous studies breast cancer risk has been increased among women who received high doses (above 100–200 cGy) of ionizing radiation or those exposed to lower doses prior to age 20. Some evidence suggests that such risk may be distinctly elevated among women with a family history of breast or ovarian cancer (probably only carriers of specific gene mutations) and women with benign breast disease (BBD).METHODS: A population-based case–control study in Los Angeles County obtained interview data from 744 women who were aged 40 or younger and diagnosed with breast cancer during 1983–1988, and from 744 matched controls. Women with a positive family history of breast or ovarian cancer reported cancer in a mother, sister, or grandmother. Women with BBD reported a physician diagnosis. Radiation exposure was defined as a history of either radiation therapy or moderate exposure to medical radiography.RESULTS: Breast cancer risk was elevated among women exposed to medical radiation prior to age 20 years (odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.2–1.8), relative to unexposed women. This increased risk was observed only among women with a history of BBD (OR = 2.4, 95% CI = 1.6–3.7). Overall, risk was not associated with exposure to medical radiation after age 20 years, although among women with a positive family history of breast or ovarian cancer, exposed women had an increased risk (OR = 1.8, 95% CI = 1.0–3.1). Breast cancer risk was not increased among women with a family history of breast/ovarian cancer exposed to medical radiation before age 20 years or those with BBD exposed to medical radiation after age 20 years.DISCUSSION: Study participants may have received radiation doses that are no longer common, hampering study generalizability. Although differences in recall between cases and controls cannot be completely excluded, women with BBD or a family history of breast cancer appear to have greater breast cancer risk following relatively low ionizing radiation exposure than other women in this study.     

Five‐year outcome of patients classified using the American Society for Radiation Oncology consensus statement guidelines for the application of accelerated partial breast irradiation

BACKGROUND:

The American Society for Radiation Oncology (ASTRO) consensus statement (CS) for the application of accelerated partial breast irradiation (APBI) was applied to patients who were treated with this technique on the American Society of Breast Surgeons MammoSite Registry Trial to determine potential differences in clinical outcome based on classification group.

METHODS:

Patients were classified based on the CS groups of “suitable,” “cautionary,” and “unsuitable.” Rates of ipsilateral breast tumor recurrence (IBTR), regional lymph node failure, distant metastases, disease‐free survival, cause‐specific survival, and overall survival were assessed.

RESULTS:

Of the 1449 cases who were treated, 1025 patients (71%) could be classified according to the CS groupings, including 419 patients (41%) who fit the “suitable” criteria, 430 patients (42%) who fit the “cautionary” criteria, and 176 patients (17%) who fit the “unsuitable” criteria. At a median follow‐up of 53.5 months, the 5‐year actuarial rates of IBTR for the “suitable,” “cautionary,” and “unsuitable” groups were 2.59%, 5.43%, and 5.28%, respectively (P = .1884). Univariate analysis of factors potentially associated with IBTR indicated that negative estrogen receptor status was the only variable associated with IBTR among patients with invasive breast cancer (odds ratio [OR], 4.01; P = .0003). Larger tumor size was associated with a greater risk of distant metastasis (OR, 3.05; P = .0001). Among patients with ductal carcinoma in situ, only age <50 years and close‐positive margins were associated with IBTR (OR, 1.12 [P = .0079] and OR, 7.81 [P = .0131], respectively).

CONCLUSIONS:

The ASTRO CS groupings did not differentiate a subset of patients with a significantly worse rate of IBTR when they were treated with the MammoSite breast brachytherapy catheter to deliver APBI. Cancer 2010. © 2010 American Cancer Society.     

Estimating single nucleotide polymorphism associations using pedigree data: applications to breast cancer

Background:

Pedigrees with multiple genotyped family members have been underutilised in breast cancer (BC) genetic-association studies. We developed a pedigree-based analytical framework to characterise single-nucleotide polymorphism (SNP) associations with BC risk using data from 736 BC families ascertained through multiple affected individuals. On average, eight family members had been genotyped for 24 SNPs previously associated with BC.

Methods:

Breast cancer incidence was modelled on the basis of SNP effects and residual polygenic effects. Relative risk (RR) estimates were obtained by maximising the retrospective likelihood (RL) of observing the family genotypes conditional on all disease phenotypes. Models were extended to assess parent-of-origin effects (POEs).

Results:

Thirteen SNPs were significantly associated with BC under the pedigree RL approach. This approach yielded estimates consistent with those from large population-based studies. Logistic regression models ignoring pedigree structure generally gave larger RRs and association P-values. SNP rs3817198 in LSP1, previously shown to exhibit POE, yielded maternal and paternal RR estimates that were similar to those previously reported (paternal RR=1.12 (95% confidence interval (CI): 0.99–1.27), P=0.081, one-sided P=0.04; maternal RR=0.94 (95% CI: 0.84–1.06), P=0.33). No other SNP exhibited POE.

Conclusion:

Our pedigree-based methods provide a valuable and efficient tool for characterising genetic associations with BC risk or other diseases and can complement population-based studies.     

Obesity is associated with breast cancer in African-American women but not Hispanic women in South Los Angeles

BACKGROUND:

Obesity is considered a risk factor for breast cancer. Modifying life styles that reduce obesity offers the potential for prevention and improved outcomes from cancer. The effects of obesity and breast cancer among African‐American women and Hispanic women have been explored in a limited number of studies. The objective of the current study was to investigate the association of obesity with breast cancer in a minority cohort.

METHODS:

This was a cross‐sectional study of 471 African‐American and Hispanic women with and without breast cancer in South Los Angeles. Data regarding body mass index (BMI) and clinical factors were obtained by medical record abstraction. Data were assessed using logistic regression with multivariate analysis. Kaplan‐Meier survival analysis was used to assess disease‐free survival.

RESULTS:

Women with breast cancer were more likely to be obese (BMI >30 kg/m²) than women without breast cancer (odds ratio [OR], 2.0; P = .01). There was a significant association of being overweight or obese and breast cancer among postmenopausal women (OR, 2.3 [P = .03] and 2.9 [P < .01], respectively). The association between obesity and breast cancer was significant only among African‐American women (OR, 2.70; P < .01) and was especially significant among postmenopausal African‐American women (OR, 4.8; P < .01). There was a borderline significant association between obesity and later disease stage at diagnosis (P = .06). An association also was observed between higher BMI (for cutoff points of both 30 kg/m² and 28 kg/m²) and poorer disease‐free survival (P = .045 and P = .019, respectively).

CONCLUSIONS:

The current data suggested an association between obesity and breast cancer, especially among postmenopausal women and most significantly in the African‐American cohort. Cancer 2011. © 2011 American Cancer Society.