Racial differences in breast carcinoma survival

BACKGROUND: Survival after breast carcinoma diagnosis is significantly worse among African American women for reasons unknown. The purpose of this study was to update reports on the National Surveillance, Epidemiology, and End Results Program and to examine the effect of race on breast carcinoma survival. METHODS: Subjects were 135,424 women diagnosed with primary breast carcinoma between 1988-1995. Patient age, tumor stage at the time of diagnosis, hormone receptor status, tumor histology, menopausal status, and survival were compared by race category. RESULTS: African American women diagnosed with breast carcinoma (n = 11,159) had a significantly increased risk of death from breast carcinoma and from all cancers compared with white women (n = 124,265), independent of the effects of other predictor variables. African American women were significantly younger at the time of diagnosis, with approximately 33% of the population age 相似文献   

Tumor biology and prognosis in black breast cancer patients: a review

American black women have a risk of developing breast cancer lower than that of American white women. but they have a worse prognosis when they do develop the disease. A major factor responsible for this discrepancy is a relatively high poverty level in the black population, with the consequent likelihood of delayed diagnosis and presentation with more advanced disease. However, breast cancer in black women also occurs at a younger age, more often is estrogen receptor-negative, and more frequently exhibits aggressive biological behavior as judged by histopathologic grade, high tumor cell proliferation rate, and altered p53 expression. Obesity, known to be associated with a poor prognosis primarily as a consequence of increased estrogen production and bioavailability, is more common in black than in white breast cancer patients. An additional factor may be an earlier age at first completed pregnancy for black women, which is associated with a reduced breast cancer risk but also a poorer prognosis. Both the epidemiologic features and the tumor biology of breast cancer in black women serve to stress the particular importance of developing effective, specifically tailored strategies for early diagnosis in this ethnic group.     

Breast cancer statistics, 2013

In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Approximately 232,340 new cases of invasive breast cancer and 39,620 breast cancer deaths are expected to occur among US women in 2013. One in 8 women in the United States will develop breast cancer in her lifetime. Breast cancer incidence rates increased slightly among African American women; decreased among Hispanic women; and were stable among whites, Asian Americans/Pacific Islanders, and American Indians/Alaska Natives from 2006 to 2010. Historically, white women have had the highest breast cancer incidence rates among women aged 40 years and older; however, incidence rates are converging among white and African American women, particularly among women aged 50 years to 59 years. Incidence rates increased for estrogen receptor‐positive breast cancers in the youngest white women, Hispanic women aged 60 years to 69 years, and all but the oldest African American women. In contrast, estrogen receptor‐negative breast cancers declined among most age and racial/ethnic groups. These divergent trends may reflect etiologic heterogeneity and the differing effects of some factors, such as obesity and parity, on risk by tumor subtype. Since 1990, breast cancer death rates have dropped by 34% and this decrease was evident in all racial/ethnic groups except American Indians/Alaska Natives. Nevertheless, survival disparities persist by race/ethnicity, with African American women having the poorest breast cancer survival of any racial/ethnic group. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high‐quality screening, diagnosis, and treatment to all segments of the population. CA Cancer J Clin 2014;64:52–62. ^© 2013 American Cancer Society, Inc.     

Early onset of breast carcinoma in African American women with poor prognostic factors.

The purpose of this study was to determine prognostic significance of age and race as independent variables and to see role of age at the onset of breast carcinoma. A retrospective study was conducted of African American and white women with breast cancer treated at SUNY-Health Science Center Brooklyn and Kings County Hospital Center from 1983 to 1993. The objective was to analyze the differences in patterns of disease onset, as related to age and prognostic factors. A total of 738 patients were analyzed for race-adjusted comparison of stage, grade, disease-free survival, and median survival. Age at the time of diagnosis was analyzed to conduct age-specific comparisons of African American (AA) and white patients. The multivariate analysis indicated that AA women develop breast cancer 10 years earlier than white women (p = 0.00001). Corrected by stage and grade, i.e., chi2 test for stage-by-stage and grade-by-grade analysis has revealed that the AA women present with higher stage (p = 0.009), increased number of positive nodes (p = 0.00007), and more estrogen receptor/ progesterone receptor-negative tumors (p = 0.005). Further studies are required to probe into the etiologic possibilities of this significant difference. The important contributing factors could be hormonal, genetic, environmental, and socioeconomic. Obesity and dietary factors also need to be evaluated. Further studies to explore genetic susceptibility by ploidy is recommended to explain this significant difference. We conclude that the onset of breast cancer among AA women occurs at a significantly younger age than in white women, and their prognostic factors are poorer.     

Mammography screening and breast cancer biology in African American women--a review

This review examines some of the key issues in early detection and breast cancer biology for African American (AA) women which contribute to their diagnoses at more advanced stages than white women, and poorer long-term prognoses. While screening mammography is considered an essential factor in eliminating these disparities, its optimal application for AAs is not fully understood. There is a paucity of information on the success with which mammography screening programs are maintained over time in the AA population, and on screening guidelines with regard to age of initiation and frequency. No randomized clinical trials targeting AA women have been reported. This type of information is critical since breast cancer in AA women occurs at younger ages, and frequently demonstrates aggressive tumor biology at diagnosis. Studies are required to determine the incidence of interval cancers in current screening programs, and the influence of the biological characteristics which are known to differ in the breast tumors of AA and white women. Recognition of molecular and cellular characteristics which identify the potential invasiveness of ductal carcinomas in situ is also required. These studies would assist in establishing the criteria for identifying the subpopulation of younger pre-menopausal AA women who would benefit from early initiation of screening. Finally, the epidemiology and biology of mammographic densities, a risk factor for breast cancer and, perhaps, markers of aggressive disease require further study in both AA and white women.     

Racial disparities in the development of breast cancer metastases among older women

BACKGROUND:

Distant metastases are the most common and lethal type of breast cancer relapse. The authors examined whether older African American breast cancer survivors were more likely to develop metastases compared with older white women. They also examined the extent to which 6 pathways explained racial disparities in the development of metastases.

METHODS:

The authors used 1992‐1999 Surveillance, Epidemiology, and End Results (SEER) data with 1991‐1999 Medicare data. They used Medicare's International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify metastases of respiratory and digestive systems, brain, bone, or other unspecified sites. The 6 pathways consisted of patient characteristics, tumor characteristics, type of treatment received, access to medical care, surveillance mammography use, and area‐level characteristics (poverty rate and percentage African American) and were obtained from the SEER or Medicare data.

RESULTS:

Of the 35,937 women, 10.5% developed metastases. In univariate analysis, African American women were 1.61 times (95% confidence interval [CI], 1.54‐1.83) more likely to develop metastasis than white women. In multivariate analysis, tumor grade, stage at diagnosis, and census‐tract percentage African American explained why African American women were more likely to develop metastases than white women (hazard ratio, 0.84; 95% CI, 0.68‐1.03).

CONCLUSIONS:

Interventions to reduce late‐stage breast cancer among African Americans also may reduce racial disparities in subsequent increased risk of developing metastasis. African Americans diagnosed with high‐grade breast cancer could be targeted to reduce their risk of metastasis. Future studies should identify specific reasons why the racial distribution in census tracts was associated with racial disparities in the risk of breast cancer metastases. Cancer 2009. © 2009 American Cancer Society.     

Disparities and survival among breast cancer patients

BACKGROUND: Although rates of survival for women with breast cancer have improved, the survival disparity between African American and white women in the United States has increased. PURPOSE: To determine whether this survival disparity persists in an insured population with access to medical care. METHODS: In this retrospective cohort study, we extracted data from the tumor registries of six nonprofit, integrated health care delivery systems affiliated with the Cancer Research Network and assessed the survival of African American (n = 2276) and white (n = 18 879) female enrollees who were diagnosed with invasive breast cancer from January 1, 1993, through December 31, 1998. Cox proportional hazards regression was used to estimate the death rate among African American women relative to that of white women after adjustment for potential explanatory factors including stage at diagnosis, tumor characteristics, and treatment. RESULTS: Five-year survival was lower for African American women (73.8%) than for white women (81.6%). African American women were less likely to have tumor characteristics with good prognosis. Controlling for age at diagnosis, stage, grade, tumor size, and estrogen and progesterone receptor status, the adjusted hazard rate ratio for African American women was 1.34 (95% confidence interval = 1.22 to 1.46). Similar risks were found among women ages 20-49 and 50 and older. Controlling for treatment slightly lowered the hazard rate ratio to 1.31 (95% confidence interval = 1.20 to 1.43). CONCLUSIONS: Among women with invasive breast cancer, being insured and having access to medical care does not eliminate the survival disparity for African American women.     

Trends in breast cancer by race and ethnicity

In this article, the American Cancer Society (ACS) describes trends in incidence, mortality, and survival rates of female breast cancer in the United States by race and ethnicity. It also provides estimates of new cases and deaths and shows trends in screening mammography. The incidence and survival data derive from the National Cancer Institute's Surveillance, Epidemiology, and End Results program; mortality data are from the National Center for Health Statistics. Approximately 211,300 new cases of invasive breast cancer, 55,700 in situ cases, and 39,800 deaths are expected to occur among women in the United States in 2003. Breast cancer incidence rates have increased among women of all races combined and white women since the early 1980s. The increasing rate in white women predominantly involves small (< or = 2 cm) and localized-stage tumors, although a small increase in the incidence of regional-stage tumors and those larger than five cm occurred since the early 1990s. The incidence rate among African American women stabilized during the 1990s for all breast cancers and for localized tumors. African American women are more likely than white women to be diagnosed with large tumors and distant-stage disease. Other racial and ethnic groups have lower incidence rates than do either white or African American women. However, the proportion of disease diagnosed at advanced stage and with larger tumor size in all minorities is greater than in white persons. Death rates decreased by 2.5% per year among white women since 1990 and by 1% per year among African American women since 1991. The disparity in mortality rates between white and African American women increased progressively between 1980 and 2000, so that by 2000 the age-standardized death rate was 32% higher in African Americans. Clinicians should be aware that 63% and 29% of breast cancers are diagnosed at local- and regional-stage disease, for which the five-year relative survival rates are 97% and 79%, respectively. This information, coupled with decreasing mortality rates and improvements in treatment, may motivate women to have regular mammographic and clinical breast examinations. Continued efforts are needed to increase the availability of high-quality mammography and treatment to all segments of the population.     

Ethnic differences in risk perception among women at increased risk for breast cancer

Summary There has been increasing interest in the role of cultural and ethnic factors in breast cancer risk perceptions and screening practices. This study examined ethnic differences in breast cancer risk perception in 112 African American and 224 white women ages 35 and older who had at least one first-degree relative diagnosed with breast cancer. These samples were matched for education and age. Data on breast cancer risk factors, risk perceptions, breast cancer worries, and breast cancer screening practices were collected through structured telephone interviews. The results show that African American women were significantly less likely than white women to report heightened perceptions of personal risk after their relative was diagnosed with breast cancer (61% vs 82%; p<.001). Despite this, African American women had significantly greater concerns about their personal risk of breast cancer and worries about their affected relative. African American women also scored significantly higher than white women on a measure of avoidance of breast cancer-related thoughts and feelings. These psychological variables were associated independently with breast cancer risk perception in multivariate models, taking precedence over demographic and risk factor predictors. Observed ethnic differences in breast cancer risk perceptions and psychological distress may be attributable to the influence of cultural factors particular to people of African descent, such as the importance of interpersonal relationships, spirituality, and time orientation. An Africentric perspective is used to interpret these findings and to provide suggestions for delivering effective breast cancer risk counseling to African American women.     

Ethnic neutropenia and treatment delay in African American women undergoing chemotherapy for early-stage breast cancer

Disparities in breast cancer survival have been observed between African American and white women. There are also known differences in mean baseline white blood cell (WBC) count among racial and ethnic groups. If the WBC count falls below conventionally defined treatment thresholds for patients undergoing adjuvant chemotherapy, reduced doses or treatment delays may occur, which could lead to race-based differences in treatment duration. We used the tumor registry at Columbia-Presbyterian Medical Center to identify 1178 women with newly diagnosed stage I and II breast cancer from whom we collected base-line information for 73 African American women and 126 age- and tumor stage-matched white women. Of these women, 43 African American and 93 white women underwent adjuvant chemotherapy. African American women had statistically significantly lower WBC counts than white women at diagnosis (6.2 x 10(9)/L for African American women versus 7.4 x 10(9)/L for white women, difference = 1.2, 95% confidence interval [CI] = 0.2 to 1.2; P =.02) and after treatment (5.3 x 10(9)/L for African American women versus 6.4 x 10(9)/L for white women, difference = 1.1, 95% CI = 0.2 to 2.5; P =.03). Overall, African American women required a statistically significantly longer duration of treatment than white women (19 weeks versus 15 weeks, respectively, difference = 4 weeks, 95% CI = 0.5 to 7.2 weeks; P =.03). The lower baseline WBC counts and longer duration of treatment for early-stage breast cancer in African American women compared with those in white women result in lower dose intensity of treatment for African American women, possibly contributing to observed racial differences in breast cancer survival.     

A perfect storm: How tumor biology,genomics, and health care delivery patterns collide to create a racial survival disparity in breast cancer and proposed interventions for change

It is well known that there is a significant racial divide in breast cancer incidence and mortality rates. African American women are less likely to be diagnosed with breast cancer than white women but are more likely to die from it. This review explores the factors that may contribute to the racial survival disparity. Consideration is paid to what is known about the role of differences in tumor biology, genomics, cancer screening, and quality of cancer care. It is argued that it is the collision of 2 forces, tumor biology and genomics, with patterns of care that leads to the breast cancer mortality gap. The delays, misuse, and underuse of treatment for African American patients are of increased significance when these patients are presenting with more aggressive forms of breast cancer. In the current climate of health care reform ushered in by the Affordable Care Act, this article also evaluates interventions to close the disparity gap. Prior interventions have been too narrowly focused on the patient rather than addressing the system and improving care across the continuum of breast cancer evaluation and treatment. Lastly, areas of future investigation and policy initiatives aimed at reducing the racial survival disparity in breast cancer are discussed. CA Cancer J Clin 2015;65: 221–238. © 2015 American Cancer Society.     

Sociocultural predictors of breast cancer risk perceptions in African American breast cancer survivors.

Although African American breast cancer survivors are at increased risk for developing breast cancer again, empirical data are not available on breast cancer risk perceptions in these women. This study characterized perceived risk of developing breast cancer in African American breast cancer survivors at risk for having a BRCA1 or BRCA1 (BRCA1/2) mutation and identified factors having significant independent associations with risk perceptions. Participants were 95 African American breast cancer survivors at an increased risk for having a BRCA1/2 mutation. Risk perceptions and sociodemographic, clinical, treatment, and sociocultural factors were collected during a structured telephone interview. Most women reported that they had the same or lower risk of developing breast cancer again compared with other women (53%); however, a substantial minority of women (47%) reported that they had a higher or much higher risk. Factors having significant independent associations with heightened risk perceptions included having a >or=10% prior probability of having a BRCA1/2 mutation [odds ratio (OR), 2.91; 95% confidence interval (95% CI), 1.09-7.72; P = 0.03] and more years of formal education (OR, 2.74; 95% CI, 1.02-7.36; P = 0.05). In addition, women who thought about the past a lot were three times more likely to report heightened risk perceptions compared with those who did not think about the past a lot (OR, 3.72; 95% CI, 1.45-9.57; P = 0.01). These results suggest that it may be important to ensure adequate risk comprehension among African American women as part of genetic counseling for inherited breast-ovarian cancer risk. Discussion of risk perceptions within the context of existing beliefs and values may facilitate this process.     

Histologic grade,stage, and survival in breast carcinoma: comparison of African American and Caucasian women

BACKGROUND: African American women have lower breast carcinoma survival rates than do Caucasian women. African American women often present with advanced-stage disease and more aggressive tumors as shown by histologic and laboratory-based prognostic factors. Aggressive tumor behavior may be responsible, at least in part, for the advanced stage and reduced survival rates. METHODS: The authors investigated the correlation between survival and histologic grade, stage of disease, and tumor size for both African American and Caucasian women who were younger than age 50 years and age 50 years and older. The authors also investigated the distribution of grade within each stage group and the distribution of grade by tumor size. African American and Caucasian women were matched by stage, tumor size, and histologic grade. Survival was represented by 6-year breast carcinoma-specific survival rates. RESULTS: Compared with Caucasian women, African American women, regardless of age, had proportionally more Grade III tumors and fewer Grade I and II tumors for all stages combined and for each individual stage group. Similarly, matched for tumor size, African American women had more Grade III tumors and fewer Grade I and II tumors compared with Caucasian women, except for tumors smaller than 1.0 cm. For nearly all combinations of stage and grade regardless of age, the 6-year breast carcinoma-specific survival rate was lower for African American women than for Caucasian women, although it did not always reach statistical significance. CONCLUSIONS: Compared with Caucasian women, African American women, regardless of age, presented with proportionally more aggressive tumors for each stage of disease and for each tumor size above 1.0 cm as revealed by the histologic grade. Higher histologic grade may be a significant contributing factor to survival disadvantage for African American women.     

Low levels of cell cycle inhibitor p27kip1 combined with high levels of Ki-67 predict shortened disease-free survival in T1 and T2 invasive breast carcinomas

Breast cancer is the second leading cause of cancer death in North American women. There is considerable need for better prognostic markers to identify those subsets of patients who would benefit from more aggressive therapy because their tumors show an increased risk of poor clinical behavior. p27kip1 is an important inhibitor of the cell cycle that acts by binding and inactivating cyclin-dependent kinases (CDKs). The aim of this study was to determine the prognostic value of loss of p27 protein in invasive breast cancer. We performed an immunohistochemical study of 147 patients with T1 and T2 invasive breast cancers and compared survival in the high p27 expressing group with that of the low p27 expressing group. On univariate analysis comparing tumor size, nodal status, Ki-67, c-erbB-2, p53 and estrogen receptor, low or absent p27kip1 is a strong predictor of reduced disease-free survival. Importantly, on multivariate analysis, the combined effect of low p27 with high Ki-67 is a stronger predictor of reduced disease-free survival than either marker alone. This simple, reliable and inexpensive assay, particularly when used in combination with Ki-67, improves the ability to predict disease recurrence and could become a useful adjunct of breast cancer evaluation to better identify high risk patients.     

Breast cancer survivors' health-related quality of life : racial differences and comparisons with noncancer controls

BACKGROUND.

Small samples with few minority women and/or the absence of comparisons to peers without cancer histories have limited previous research suggesting racial differences in breast cancer survivors' health‐related quality of life (HRQoL). This study not only compared HRQoL of African American and white breast cancer survivors, but also compared the HRQoL of these women to that of same‐race women with no cancer history.

METHODS.

Data from the Women's Health Initiative‐Observational Study were used, including 5021 cancer survivors and 88,532 women without a history of cancer. Multivariate regression analyses estimated differences in breast cancer survivors' baseline HRQoL (RAND36), depressive symptoms (CES‐D short‐form), and sleep quality (WHIIRS).

RESULTS.

African American breast cancer survivors reported worse physical functioning and general health compared with white survivors. Among African Americans, survivors reported worse role limitations due to physical health, pain, general health, and vitality than women without a history of cancer. This was most evident in those with more recent diagnoses. Most significant differences between groups were small in magnitude (Cohen d = .21‐.36).

CONCLUSIONS.

These results add to the increasing knowledge of cancer disparities by showing that African American women have small, but clinically meaningful, decrements in physical HRQoL compared with white survivors and with African American women without cancer. Because African American women also face diagnosis with higher grade tumors and higher breast cancer mortality, more research is needed to examine the physical and psychosocial experiences of African American breast cancer survivors to elucidate the mechanisms leading to poorer outcomes. Cancer 2008. © 2008 American Cancer Society.     

Long-term outcomes among African–American and white women with breast cancer: What is the impact of comorbidity?

ObjectivesWe examined the association between comorbidity and long-term mortality from breast cancer and other causes among African–American and white women with breast cancer.MethodsA total of 170 African–American and 829 white women aged 40–84 years were followed for up to 28 years with median follow-up of 11.3 years in the Health and Functioning in Women (HFW) study. The impact of the Charlson Comorbidity Score (CCS) in the first few months following breast cancer diagnosis on the risk of mortality from breast cancer and other causes was examined using extended Cox models.ResultsMedian follow-up was significantly shorter for African–American women than their white counterparts (median 8.5 years vs. 12.3 years). Compared to white women, African–American women had significantly fewer years of education, greater body mass index, were more likely to have functional limitations and later stage at breast cancer diagnosis, and fewer had adequate financial resources (all P < 0.05). Proportionately more African–American women died of breast cancer than white women (37.1% vs. 31.4%, P = 0.15). A positive and statistically significant time-varying effect of the Charlson Comorbidity Score (CCS) on other-cause mortality persisted throughout the first 5 years of follow-up (P < 0.001) but not for its remainder.ConclusionsHigher CCS was associated with increased risk of other-cause mortality, but not breast cancer specific mortality; the association did not differ among African–American and white women.     

Alcohol intake and invasive breast cancer risk by molecular subtype and race in the Carolina Breast Cancer Study

Purpose

Alcohol is an established breast cancer risk factor, but there is little evidence on whether the association differs between African Americans and whites.

Methods

Invasive breast cancers (n = 1,795; 1,014 white, 781 African American) and age- and race-matched controls (n = 1,558; 844 white, 714 African American) from the Carolina Breast Cancer Study (Phases I–II) were used to estimate odds ratios (ORs) and 95 % confidence interval (CI) for pre-diagnosis drinks per week and breast cancer risk.

Results

African American controls reported lower alcohol intake than white controls across all age groups. Light drinking (0 to ≤2 per week) was more prevalent among African American controls. Moderate-to-heavy drinking was more prevalent in white controls. African Americans who reported drinking >7 drinks per week had an elevated risk compared to light drinkers [adjusted OR, 95% CI 1.62 (1.03–2.54)]. A weaker association was observed among whites [adjusted OR, 95% CI 1.20 (0.87–1.67)]. The association of >7 drinks per week with estrogen receptor-negative [adjusted OR, 95% CI 2.17 (1.25–3.75)] and triple-negative [adjusted OR, 95% CI 2.12 (1.12–4.04)] breast cancers was significant for African American, but not white women. We observed significantly elevated ORs for heavy intake at ages <25 and >50 years of age for African American women only. We found no evidence of statistical interaction between alcohol intake and oral contraceptive use or smoking.

Conclusions

Drinking more than seven alcoholic beverages per week increased invasive breast cancer risk among white and African American women, with significant increases only among African American women. Genetic or environmental factors that differ by race may mediate the alcohol–breast cancer risk association.

     

Brief report: etiological attributions for breast cancer among healthy African American and European American women

Anecdotal evidence suggests that African American women's attributions about breast cancer may differ from European American women, but empirical studies are lacking. The present study examined attributions about breast cancer made by a sample of healthy African American and European American women. The sample included 197 women (75 African American, 122 European American), with a mean age of 39.2. Overall, women were most likely to attribute the development of breast cancer to genetics, "no one", environmental poisons, diet, personal behavior and stress. European American women were more likely to attribute breast cancer to broadly external causes such as the environment, heredity and chance, while African American women were more likely to list immediate, interpersonal-level causes such as a blow to the breast, and personal behavior. Results highlight the need for attention to cultural processes in cancer prevention and control.     

Polymorphisms in nucleotide excision repair genes, smoking and breast cancer in African Americans and whites: a population-based case-control study

Polymorphisms exist in several genes involved in nucleotide excision repair (NER), the principal pathway for removal of smoking-induced DNA damage. An epidemiologic study was conducted to determine whether these polymorphisms modify the association between smoking and breast cancer. DNA samples and exposure histories were analyzed as part of a large population-based case-control study of breast cancer in North Carolina. The study population included 2311 cases (894 African Americans, 1417 whites) and 2022 controls (788 African Americans, 1234 whites). Odds ratios (ORs) were calculated for breast cancer and smoking, and for breast cancer and nine non-synonymous coding polymorphisms in six NER genes (XPD codons 312 and 751, RAD23B codon 249, XPG codon 1104, XPC codon 939, XPF codons 415 and 662, and ERCC6 codons 1213 and 1230). Modification of ORs for smoking by single and combined NER genotypes was investigated. In this study population, smoking was more strongly associated with breast cancer in African American women compared with white women. Among African American women, the association of breast cancer and smoking was strongest among women with specific combinations of NER genotypes. Evidence for multiplicative interaction was found between combined NER genotypes and smoking dose (likelihood ratio test P = 0.06), duration (P = 0.09), time since cessation (P = 0.02), age at initiation (P = 0.04) and former smoking (P = 0.03). No interactions were observed in white women. Therefore, polymorphisms in NER genes may modify the relationship between breast cancer and smoking. These results are consistent with previous evidence of exposure-specific p53 mutations in breast tumors from current and former smokers, suggesting that smoking may play a role in breast cancer etiology.