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BACKGROUND: The incidence of testicular germ cell tumors (TGCTs) has been increasing the past 4 to 6 decades; however, exposures that account for this rise have not been identified. Marijuana use also grew during the same period, and it has been established that chronic marijuana use produces adverse effects on the human endocrine and reproductive systems. In this study, the authors tested the hypothesis that marijuana use is a risk factor for TGCT. METHODS: A population-based, case-control study of 369 men ages 18 to 44 years who were diagnosed with TGCT from January 1999 through January 2006 was conducted in King, Pierce and Snohomish Counties in Washington State. The responses of these men to questions on their lifetime marijuana use were compared with the responses of 979 age-matched controls who resided in the same 3 counties during the case diagnosis period. RESULTS: Men with a TGCT were more likely to be current marijuana smokers at the reference date compared with controls (odds ratio [OR], 1.7; 95% confidence interval [95% CI], 1.1-2.5). In analyses according to histologic type, most of the association between current marijuana use and TGCT was observed in men who had nonseminomas/mixed histology tumors (current use: OR, 2.3; 95% CI, 1.3-4.0). Age at first use among current users (age

Molecular profiling studies have identified subtypes of breast cancer that can be approximately classified by estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu (HER-2) expression. These molecular subtypes are prognostically significant, but to the authors' knowledge, differences in their etiologic profiles have not been established. Reproductive factors may plausibly be differentially correlated with the risk of different breast cancer subtypes because these factors are presumed to impact exposure to endogenous sex hormones.The authors pooled 2 population-based, case-control studies of breast cancer in women ages 55 to 79 years for an analysis including 1476 controls and 1023 cases of luminal breast cancer, 39 cases of HER-2-overexpressing breast cancer, and 78 cases of triple-negative breast cancer. Polytomous logistic regression was used to compare each case group with controls.Associations varied by molecular subtype. Early age at menarche was only found to be associated with risk of HER-2-overexpressing disease (odds ratio [OR] of 2.7; 95% confidence interval [95% CI], 1.4-5.5), whereas breastfeeding foror =6 months was only found to be protective for luminal and triple-negative disease (OR of 0.8 [95% CI, 0.6-1.0] and OR of 0.5 [95% CI, 0.3-0.9], respectively). Both late age at menopause and the use of estrogen plus progestin hormone therapy were only found to be associated with risk of luminal disease (OR of 1.6 [95% CI, 1.1-2.2] and OR of 1.7 [95% CI, 1.3-2.1], respectively). No differences in risks associated with parity or age at first live birth were observed by subtype.Certain reproductive factors may have a greater impact on the risk of certain molecular subtypes of disease compared with others. Future studies that further define the etiology of breast cancer subtypes will add to the biologic understanding of this disease.

BACKGROUND Incidence rates of ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) have been rising, but little is known about which patients will develop invasive breast cancer or what types of tumors these patients may develop. METHODS By using Surveillance, Epidemiology and End Results (SEER) data, the authors evaluated how types of invasive breast cancers diagnosed among 37,692 DCIS and 4490 LCIS patients differed and how clinical characteristics influenced subsequent breast cancer risk. RESULTS Among DCIS patients, incidence rates of ipsilateral and contralateral invasive breast cancer were 5.4/1000 person-years and 4.5/1000 person-years, respectively; and among LCIS patients, incidence rates were 7.3/1000 person-years and 5.2/1000 person-years, respectively. LCIS patients were 5.3-fold more likely than DCIS patients to develop invasive lobular carcinomas. Women whose DCIS had comedo histologic features or was poorly differentiated had 1.4-fold and 2.0-fold elevations in ipsilateral invasive breast cancer risk. Furthermore, among DCIS patients, 20-49 year-olds and black women and Hispanic white women had 1.6, 2.7, and 2.3-fold elevated risks of Stage III/IV breast cancer compared with 50-59 year-olds and non-Hispanic whites, respectively. CONCLUSIONS Screening young DCIS patients more frequently and improving the follow-up care of blacks and Hispanic whites with DCIS may reduce their risk of advanced-stage breast cancer. In addition, LCIS may be a precursor rather than just an ambiguous risk factor for invasive breast cancer, and, therefore, localized treatment for LCIS may be warranted. Given that incidence rates of DCIS and LCIS have been rising, investigations of these tumors should be continued to better understand their etiology and appropriate clinical management. Cancer 2006. © 2006 American Cancer Society.

BACKGROUND. The incidence of anal cancer has increased among both men (160%) and women (78%) from 1973 to 2000 in the U.S. The authors conducted a population-based case– control study of anal cancer to examine factors that may account for this increase. METHODS. Men (n 119 patients) and women (n 187 patients) who were diagnosed with anal cancer between 1986 and 1998 in the Seattle area were ascertained through the local Surveillance, Epidemiology, and End Results registry. Control participants (n 1700) were ascertained through random-digit telephone dialing. Participants were interviewed in person and provided blood samples. Archival tumor tissue was tested for human papilloma virus (HPV) DNA, and serum samples were tested for HPV type 16 (HPV-16). RESULTS. Overall, 88% of tumors (all histologies) in the study were found to be positive for HPV. HPV-16 was the most frequent HPV type detected (73% of all tumors), followed by HPV-18 (6.9%), regardless of gender. However, 97.7% of tumors from men who were not exclusively heterosexual contained HPV DNA. The risk of anal cancer increased among men (odds ratio [OR], 5.3; 95% confidence interval [95% CI], 2.4 –12.0) and women (OR, 11.0; 95% CI, 5.5–22.1) who had 15 sexual partners during their lifetime. Among men who were not exclusively heterosexual and women, receptive anal intercourse was related strongly to the risk of anal cancer (OR, 6.8 [95% CI, 1.4 –33.8] and OR, 2.2 [95% CI, 1.4 –3.3], respectively). Current smokers among men and women were at particularly high risk for anal cancer, independent of age and other risk factors (OR, 3.9 [95% CI, 1.9 – 8.0] and OR, 3.8 [95% CI, 2.4 – 6.2], respectively). CONCLUSIONS. The high proportion of tumors with detectable HPV suggests that infection with HPV is a necessary cause of anal cancer, similar to that of cervical cancer. Increases in the prevalence of exposures, such as cigarette smoking, anal intercourse, HPV infection, and the number of lifetime sexual partners, may account for the increasing incidence of anal cancer in men and women. Cancer 2004;101:270 – 80. © 2004 American Cancer Society.

BACKGROUND. Anal cancer is a rare malignancy of the anogenital tract that historically has affected women at a greater rate than men. METHODS. The authors analyzed changing trends in incidence rates and 5-year relative survival percentages for patients with anal cancer. The publicly available data used in the current study were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program, a system of population-based tumor registries in the United States. RESULTS. The incidence of anal cancer was similar for men and women between 1994 and 2000 (2.04 per 100,000 and 2.06 per 100,000, respectively), the most recent period for which data were available, whereas men had lower rates than did women between 1973 and 1979 (1.06 per 100,000, compared with 1.39 per 100,000), the earliest period for which data were available. In addition, recently, black men had higher incidence rates than did other race-specific and gender-specific groups (2.71 per 100,000). From the earliest period for which data were available to the most recent period, relative 5-year survival improved from 59% to 73% among women, was unchanged among men (60%), and decreased from 45% to 27% among black men. Eighteen percent of patients who had distant disease were alive at 5 years, compared with 78% of patients who had localized disease. CONCLUSIONS. The incidence of anal cancer in the United States increased between 1973 and 2000, particularly among men. There were higher incidence rates and lower survival rates for black men compared with other race-specific and gender-specific groups. Later disease stage was inversely associated with the survival rate, indicating that earlier detection may improve the survival of patients with anal cancer. Cancer 2004;101:281– 8. © 2004 American Cancer Society.

BACKGROUND Few studies have investigated the association between reproductive factors and the risk of breast carcinoma among African-American women. The authors assessed whether the number of full-term pregnancies, age at first full-term pregnancy, and total duration of breastfeeding were associated with similar relative risk estimates in white and African-American women in a large multicenter, population-based case–control study of breast carcinoma. METHODS Case patients were 4567 women (2950 white women and 1617 African-American women) ages 35–64 years with newly diagnosed invasive breast carcinoma between 1994 and 1998. Control patients were 4668 women (3012 white women and 1656 African-American women) who were identified by random-digit dialing and were frequency matched to case patients according to study center, race, and age. Adjusted odds ratios and 95% confidence intervals were estimated using unconditional logistic regression. RESULTS For white women, the reduction in risk of breast carcinoma per full-term pregnancy was 13% among younger women (ages 35–49 years) and 10% among older women (ages 50–64 years). The corresponding risk reductions for African-American women were 10% and 6%, respectively. Risk decreased significantly with increasing number of full-term pregnancies for both races and both age categories. Duration of lactation was inversely associated with breast carcinoma risk among younger parous white (trend P = 0.0001) and African-American (trend P = 0.01) women. African-American women tended to have more children compared with white women, but parity rates were lower in younger women than in older women in both racial groups. However, breastfeeding was substantially more common in young white women than in young African-American women. CONCLUSIONS Overall, parity and lactation had similar effects on breast carcinoma risk in white and African-American women. If younger African-American women now are giving birth to fewer children than in the past, without a substantial increase in breastfeeding, breast carcinoma rates may continue to increase at a more rapid rate among these women compared with white women. Cancer 2004. Published 2004 by the American Cancer Society.

BACKGROUND Limited data are available regarding the incidence of breast carcinoma among users of relatively recently introduced forms of antihypertensive therapy. Although it has been suggested that women who have taken calcium channel blockers (CCBs) have an increased risk and that women who have taken angiotensin-I-converting enzyme (ACE) inhibitors have a decreased risk, currently, no conclusions can be drawn. METHODS A population-based case–control study of women ages 65–79 years was conducted in western Washington State. The responses of 975 women who were diagnosed with invasive breast carcinoma during 1997–1999 were compared with the responses of 1007 women in a control group. Associations between use of different types of antihypertensive medications and breast carcinoma incidence were evaluated using logistic regression. RESULTS Overall, women who had ever used CCBs, β-blockers, or ACE inhibitors did not have an altered risk of breast carcinoma relative to women who had never used antihypertensive medications. Although the use of immediate-release CCBs, thiazide diuretics, and potassium-sparing diuretics was associated with modestly increased risks of breast carcinoma (odds ratio [OR], 1.5; 95% confidence interval [95% CI], 1.0–2.1; OR, 1.4; 95% CI, 1.1–1.8; and OR, 1.6; 95% CI, 1.2–2.1, respectively), the absence of any trend in the size of excess risk with increasing duration or with current versus former use of these agents argues for a cautious interpretation. CONCLUSIONS The use of particular types of antihypertensive medications, including immediate-release CCBs and certain diuretics, may increase the risk of breast carcinoma among older women. Additional studies are warranted to clarify these potential associations. Cancer 2003;98:1504–13. © 2003 American Cancer Society. DOI 10.1002/cncr.11663

BACKGROUND The association between method of detection and breast carcinoma histopathology has not been assessed adequately in a population-based setting. METHODS Among women who were included in a population-based, case-control study of breast cancer, patients who were newly diagnosed with invasive breast carcinoma were identified from Wisconsin's statewide tumor registry. Only women age ≥ 50 years were analyzed, because screening by mammography was not recommended before age 50 years at the time of the study. The breast tumors among these women (n = 2341 tumors) included the following histopathologies: lobular carcinoma (n = 206 tumors); ductal carcinoma, not otherwise specified (n = 1920 tumors); papillary carcinoma (n = 15 tumors); medullary carcinoma (n = 36 tumors); mucinous adenocarcinoma (n = 56 tumors); tubular adenocarcinoma (n = 41 tumors); invasive comedocarcinoma (n = 24 tumors); scirrhous adenocarcinoma (n = 15 tumors); and mixed ductal/lobular carcinoma (n = 28 tumors). RESULTS Overall, women reported that 41% of tumors were detected by mammography, 48% of tumors were self detected, and 11% of tumors were detected by clinical breast examination (CBE). Detection by mammography was significantly more likely for women who had tubular carcinoma (83%; P < 0.001) and invasive comedocarcinoma (67%; P = 0.23) compared with women who had ductal carcinoma (40%). Mammography was significantly less likely to detect medullary carcinoma (17%) than ductal carcinoma (40%; P = 0.01). Lobular carcinoma was the only histopathology that, compared with ductal carcinoma, was detected significantly more often by CBE than by self detection. Mammography detected lobular carcinoma (42%) as frequently as ductal carcinoma (40%). However, the use of postmenopausal hormones may have modified these detection patterns: Among current users, mammography discovered a greater percentage of ductal carcinomas (51%) and fewer lobular carcinomas (36%) than nonusers. CONCLUSIONS Among women age ≥ 50 years, breast cancer detection by mammography, self detection, and CBE varied according to tumor histopathology. Cancer 2002;95:470–7. © 2002 American Cancer Society. DOI 10.1002/cncr.10695

BACKGROUND Obesity has been shown to affect breast carcinoma prognosis, with the heaviest women having a higher mortality due to breast carcinoma. Few studies have focused on premenopausal women or the correlation of body mass index (BMI) to tumor characteristics related to prognosis. METHODS The authors conducted a population-based follow-up study for mortality of 1177 women younger than 45 years of age who had invasive ductal breast carcinoma diagnosed from 1983 through 1992. Histologic slides and/or tumor tissue were collected for pathologic review, immunohistochemistry assays, and bivariate flow cytometric analysis. RESULTS Women with breast carcinoma who were in the highest quartile of BMI were 2.5 times as likely (95% confidence interval [CI], 1.6–3.9) to die of their disease within 5 years of diagnosis compared with women in the lowest quartile of BMI. The tumors of the women in the highest quartile of BMI were more likely to be estrogen receptor negative (odds ratio [OR], 1.5; 95% CI, 1.0–2.2) and to have a high S-phase fraction (OR, 1.9; 95% CI, 1.2–3.1), high histologic grade (OR, 1.7; 95% CI, 1.0–2.9), high mitotic cell count (OR, 2.0; 95% CI, 1.2–3.1), and large tumor size (2 to < 5 cm: OR, 2.3; 95% CI, 1.5–3.1; or ≥ 5 cm: OR, 2.7; 95% CI, 1.5–4.8) compared with the tumors of women whose BMI was in the first quartile. Relative to the large tumors (≥ 2 cm) in women in the lowest BMI quartile, the large tumors in women in the highest BMI quartile were more likely to express markers of high proliferation, indicating they may have grown faster than similar size tumors of the thinnest women. In a multivariate analysis including the tumor characteristics, obesity, as measured by being in the highest quartile of BMI, remained an independent prognostic factor for mortality (hazard ratio, 1.7; 95% CI, 1.0–2.9; P < 0.05. CONCLUSIONS Our study results indicated that being in the highest quartile of BMI was a strong predictor of mortality in women with breast carcinoma diagnosed at a young age. The tumors of the heavy women were larger and more likely to have markers of high cellular proliferation than those of thinner women. Cancer 2001;92:720–9. © 2001 American Cancer Society.

BACKGROUND An increased incidence of breast carcinoma has been reported among relatives of individuals who are affected with the rare recessive disorder, ataxia-telangiectasia (A-T), and who are heterozygous for mutations in the ataxia-telangiectasia mutated (ATM) gene. However, most studies of breast carcinoma cases from the general population have failed to find a higher incidence of ATM mutations in cases when compared with controls. METHODS Genomic DNA samples from 258 individuals were screened for mutations of all types in each of the 62 coding exons of the ATM gene; 142 of these were from breast carcinoma cases with a first-degree family history or early age at diagnosis, 35 were from cases selected for the presence of either known disease-related mutations (n = 25) or missense alterations of unknown consequences (n = 10) in BRCA1 or BRCA2, and 81 were from matched controls. RESULTS A total of 12 individuals with ATM mutations were identified, 11 among 142 breast carcinoma cases (7.7%; 95% CI, 3.9–13.4%) and 1 among 81 controls (1.2%; 95% CI, 0.0–6.7%) (P = 0.06). All mutations detected were of the missense type; none were predicted to truncate the ATM protein. Among cases, mutations were found exclusively in patients with a family history of breast carcinoma (12.1%; 95% CI, 6.2–20.6%) (P = 0.02). Similar frequencies of ATM mutations were found in 35 additional cases selected for the presence of BRCA1 or BRCA2 mutations when compared with cases overall. CONCLUSIONS ATM mutations, specifically missense mutations, are more common in breast carcinoma cases selected for first-degree family history and early age at diagnosis. Cancer 2001;92:479–87. © 2001 American Cancer Society.

BACKGROUND In 1998, an unusually large number of invasive lobular breast carcinoma cases were seen at the University of Washington. The purpose of this study was to assess whether the incidence rate of invasive lobular carcinoma has been increasing disproportionately compared with the incidence rate of invasive ductal carcinoma. METHODS Age specific and age-adjusted breast carcinoma incidence rates from 1977–1995 were obtained from the nine population-based cancer registries that participate in the Surveillance, Epidemiology, and End Results (SEER) program. Three histologic groupings were used: lobular, ductal, and all invasive breast carcinomas. Overall incidence rates for each grouping, as well as for each stage (local, regional, and distant), were obtained. RESULTS The rate of incidence of lobular carcinoma increased steadily from 1977–1995 in women age ≥ 50 years whereas it remained stable in women age < 50 years. Alternatively, the rate of incidence of ductal carcinoma increased steadily from 1977–1987, but from 1987–1995 it remained relatively constant across all age groups. CONCLUSIONS The incidence rates of invasive lobular breast carcinomas increased steadily since 1977 whereas the incidence rates of invasive ductal carcinoma have plateaued since 1987. This rise occurred specifically among women age ≥ 50 years and may be related to postmenopausal status. Further epidemiologic, clinical, and laboratory research is required to assess what factors are contributing to this trend. Cancer 2000;88:2561–9. © 2000 American Cancer Society.

BACKGROUND There is a clear and growing need for data regarding BRCA1 and BRCA2 mutation frequencies among breast carcinoma cases not specifically ascertained on the basis of extreme family history profiles. Toward this end, the authors previously reported results with regard to BRCA1 in breast carcinoma patients drawn from a population-based study. In the current study the authors present new findings concerning BRCA2 mutation frequency in this same population, as well as summary data regarding the combined contribution of these two genes. METHODS Subjects were drawn from two population-based, case-control studies of breast carcinoma in young women conducted in western Washington State and focused on 1) women diagnosed with breast carcinoma before age 35 years (n = 203); and 2) women with a first-degree family history of breast carcinoma who were diagnosed before age 45 years (n = 225). Similarities and differences between BRCA2 carriers and BRCA1 carriers were analyzed in terms of age at diagnosis, family history status, and disease features. RESULTS Of cases diagnosed before age 35 years, all of whom were unselected for family history, 9.4% carried germline mutations (3.4% for BRCA2 and 5.9% for BRCA1). Of cases diagnosed before age 45 years who had a first-degree family history of breast carcinoma, 12.0% carried germline mutations (4.9% for BRCA2 and 7.1% for BRCA1). Increased frequencies of mutations were observed in cases with a personal or family history of early age at diagnosis and in those with four or more family members affected with breast carcinoma. BRCA2 mutations were less common than BRCA1 mutations in families with any history of ovarian carcinoma. CONCLUSIONS Overall, given current constraints on health care resources, these data suggest that screening for germline mutations in these breast carcinoma susceptibility genes may have the greatest impact on overall health care if it is prioritized toward high and moderate risk populations. Cancer 2000;88:1393–1402. © 2000 American Cancer Society.

BACKGROUND To the authors' knowledge, no previous studies have identified an adverse effect of pregnancy on patient survival after breast carcinoma. However, results are difficult to interpret because of failure to control for stage of disease at the time the pregnancy occurred. METHODS Study participants were women diagnosed with invasive breast carcinoma between 1983–1992 who previously had participated in a population-based case–control study or, if deceased, proxy respondents. Information regarding subsequent pregnancies was obtained by self-administered questionnaire or telephone interview. Information regarding breast carcinoma recurrences was obtained by questionnaire and from cancer registry abstracts. Women who became pregnant after a diagnosis of breast carcinoma (n = 53) were matched with women without subsequent pregnancies based on stage of disease at diagnosis and a recurrence free survival time in the comparison women greater than or equal to the interval between breast carcinoma diagnosis and onset of pregnancy in the women with a subsequent pregnancy. RESULTS Sixty-eight percent of women who became pregnant after being diagnosed with breast carcinoma delivered one or more live-born infants. Miscarriages occurred in 24% of the patients who became pregnant compared with 18% of the controls (women without breast carcinoma) of similar ages from the case–control study. Five of the 53 women who had been pregnant after breast carcinoma died of the disease. The age-adjusted relative risk (RR) of death associated with any subsequent pregnancy was 0.8 (95% confidence interval [95% CI], 0.3–2.3). All five deaths occurred among the 36 women who had a live birth (age-adjusted RR = 1.1; 95% CI, 0.4–3.7). CONCLUSIONS The findings of the current study are based on a small number of deaths but do not suggest that pregnancy after a diagnosis of breast carcinoma has an adverse effect on survival. [See editorial on pages 2301–4, this issue.] Cancer 1999;85:2424–32. © 1999 American Cancer Society.

BACKGROUND The use of calcium channel blockers in an elderly population recently was reported to be associated with the incidence of cancer. The Cardiovascular Health Study, a multisite observational cohort study, provided the opportunity to investigate the epidemiologic association between the use of calcium channel blockers and breast carcinoma risk in 3198 women age ≥ 65 years. METHODS Standard questionnaires and clinical procedures were administered at four study sites annually from 1989-1990 to 1993-1994. Drug usage was assessed by a medication inventory and hospitalizations for 75 incident invasive breast carcinoma cases were identified using International Classification of Diseases-9 Clinical Modification codes. Time-dependent Cox proportional hazards regression models were used to assess associations between incident breast carcinoma and the use of specific antihypertensive medication including calcium channel blockers. RESULTS In adjusted Cox proportional hazards models, an elevated risk of breast carcinoma was associated with use of calcium channel blockers (hazard ratio [HR]: 2.57; 95% confidence interval [CI], 1.47-4.49). This association persisted when the comparison group was users of other antihypertensive medication. No associations between the use of other antihypertensive medication with incident breast carcinoma were found. Associations were enhanced by assessment of high dose at baseline (HR: 4.42; 95% CI, 1.37-14.27) and when calcium channel blockers were combined with estrogen use (HR: 4.48; 95% CI, 1.58-12.75). The association was found to be strongest for the use of estrogens with immediate release calcium channel blockers (HR: 8.48; 95% CI, 2.99-24.08). CONCLUSIONS Although the number of cases was limited in this observational study, associations found between the use of calcium channel blockers and incident invasive breast carcinoma warrant further investigation. Site specific carcinomas should be included as an outcome of ongoing and planned long term clinical trials using calcium channel blockers. Cancer 1997; 80:1438-47. © 1997 American Cancer Society.

BACKGROUND This study investigates whether a positive family history of breast carcinoma is associated with improved survival after invasive breast carcinoma among women ages 21 through 45. METHODS Subjects were 733 nonadopted women born after 1944 who were diagnosed with primary invasive breast carcinoma between January 1983 and April 1990 while residing in the metropolitan Seattle area and who provided information on family history of breast carcinoma. Information on clinical characteristics and survival was obtained from a population-based cancer registry. Subjects were followed for survival through 1994. Cox proportional hazards models were used to estimate the relative risk (RR) of dying in relation to family history of breast carcinoma, adjusting for selected clinical characteristics, age and year of diagnosis, and prior mammograms. RESULTS The risk of dying among women with a first-degree family history of breast carcinoma was half that of women with no family history of breast carcinoma (RR = 0.5; 95% confidence interval [CI], 0.3–0.9). There was no evidence of a reduction in the risk of dying among women with only a second-degree family history of breast carcinoma (RR = 1; 95% CI, 0.6–1.4). These associations were adjusted for age and year of diagnosis, stage of disease, tumor size, bilaterality, and mammogram history. These findings were not further influenced by adjustment for initial treatment or the numbers and ages of relatives at risk for breast carcinoma. CONCLUSIONS Compared with women with neither a first- nor second-degree family history of breast carcinoma, the authors found that women who had a first-degree family history experienced increased survival. This finding did not appear to be attributable to differences in screening or treatment. To the extent that this difference is attributable to underlying biologic mechanisms, new insights into the natural history and treatment of breast carcinoma could result. Future studies should investigate whether specific susceptibility genes are associated with differential survival from breast carcinoma. Cancer 1996;78:1417-25.

BACKGROUND We analyzed data from a population-based, multi-center, case-control study to determine whether the occurrence of histologic types of uterine sarcoma is related to exogenous hormone use and/or to two correlates of endogenous estrogens: excess weight and cigarette smoking. METHODS One hundred sixty-seven women with newly-diagnosed uterine sarcoma (56 leiomyosarcoma, 85 mixed mullerian tumors, and 26 endometrial stromal sarcomas) were interviewed by telephone regarding possible risk factors for these neoplasms. For comparison, 208 women identified at random from the general population of the study areas were interviewed as controls. RESULTS Use of oral contraceptives was positively associated with the risk of leiomyosarcoma (odds ratios [OR] = 1.7, 95% confidence interval [CI] = 0.7, 4.1), primarily among women who last used these medications 15 or more years prior to diagnosis. Use of noncontraceptive estrogens was directly associated with the risk of mixed mullerian tumors, but only among recent and long-term users of these medications. Women in the highest quantile of body mass index (;ce 27.5 kg/m2) one year prior to diagnosis were at increased risk of each type of uterine sarcoma (leiomyosarcoma, OR = 2.5, 95% CI = 1.1, 5.7; mixed mullerian tumors, OR = 2.9, 95% CI = 1.3, 6.7; stromal sarcoma, OR = 3.5, 95% CI = 1.1, 10.9). Women who had ever smoked cigarettes were at reduced risk of leiomyosarcoma (OR = 0.6, 95% CI = 0.3, 1.1) and stromal sarcoma (OR = 0.5, 95% CI = 0.2, 1.2), but the relationship was not more pronounced among heavy smokers; no association with smoking was observed with mixed mullerian tumors. CONCLUSIONS Several of these findings parallel those from studies of endometrial carcinoma, and may indicate a role for unopposed estrogen in the etiology of histologic types of uterine sarcoma. Cancer 1996;77:717-24.

BACKGROUND Statin use has increased dramatically in the U.S. in the past decade. Animal and mechanistic studies suggested that statins may have an inhibitory effect on cancer proliferation, including breast carcinoma. However, statins have been found to be carcinogenic in rodents and one clinical trial found an excess of breast carcinoma cases in the treatment group. METHODS The current study assessed whether the use of statins altered the risk of breast carcinoma in older women. The population-based, case–control study comprised female residents from three western Washington State counties. Cases included 975 women identified from the Cancer Surveillance System who were diagnosed with primary invasive breast carcinoma between 1997–1999, whose names appeared on a list of Social Security recipients provided by the Centers for Medicare and Medicaid Services. The cases were ages 65–79 years at the time of diagnosis. The comparison group was comprised of 1007 women without breast carcinoma who were randomly selected from the same list of Social Security recipients. Information pertaining to statin use, medical history, and health behaviors was ascertained through an in-person interview. RESULTS Compared with nonusers, women who were currently using statins or had ever used statins were not found to be at an increased risk for breast carcinoma (odds ratios [OR] = 0.9; 95% confidence interval [95% CI], 0.7–1.2). There was some indication that long-term statin use (> 5 years) was related to a slight decrease in breast carcinoma risk (OR = 0.7; 95% CI, 0.4–1.0). CONCLUSIONS The results of the current study provided some degree of reassurance to the increasing numbers of women using statins that such use is not associated with an increased risk of breast carcinoma. Although the data gave some support to a reduced risk of breast carcinoma among long-term users of statins, further research is needed to confirm this association. Cancer 2004. © 2004 American Cancer Society.

BACKGROUND Many young patients with breast carcinoma have not started, or completed, their desired families. How childbearing after a diagnosis of breast carcinoma affects survival is of importance to these women and their families. The authors measured relative mortality among young patients with breast carcinoma with and without births occurring after diagnosis. METHODS The authors conducted a cohort study using data from three population-based cancer registries in the U.S. (Seattle, Detroit, and Los Angeles), linked to birth certificate data in each state. Four hundred thirty-eight women younger than 45 years of age with primary invasive breast carcinoma were identified as having births after diagnosis. In addition, 2775 comparison women, matched on the basis of age at the time of diagnosis, race/ethnicity, diagnosis year, disease stage, and presence of previous nonbreast primary tumors, were identified among those with breast carcinoma without births after diagnosis. Relative mortality was assessed using multivariable statistical methods. RESULTS After adjustment for stage of disease, age at diagnosis, study region, diagnosis year, and race/ethnicity, women with births occurring 10 months or more after diagnosis had a significantly decreased risk of dying (relative Risk [RR] = 0.54, 95% confidence interval [CI], 0.41–0.71) compared to women without subsequent births. Women pregnant at the time of diagnosis had a mortality rate similar to those who did not give birth (RR = 1.10, 95% CI, 0.80–1.60). CONCLUSIONS The results of the current study, in light of growing evidence from other studies using various methods, may provide some reassurance to young women with breast carcinoma that subsequent childbearing is unlikely to increase their risk of mortality. Cancer 2003;98:1131–40. © 2003 American Cancer Society. DOI 10.1002/cncr.11634

We read with great interest the article by Phipps et al in which they examined the risk factors for different subtypes of postmenopausal breast cancer. They found that certain reproductive factors have a greater effect on the risk of certain molecular subtypes of disease compared with others. However the authors did not analyze oral contraceptive use as a risk factor. Oral contraceptive use has been associated with an increased risk of breast cancer in young women. Narod et al demonstrated that among BRCA1 mutation carriers women who first used oral contraceptives before 1975 who used them before age 30 years or who used them for > or = 5 years may have an increased risk of developing breast cancer. Sporadic triple-negative breast cancers and tumors that are noted in carriers of the BRCA1 mutation share similar features including estrogen receptor negativity high nuclear grade high Ki-67 staining cytokeratin 5/6 expression and epidermal growth factor receptor expression. Furthermore BRCA1 is rarely mutated in sporadic breast cancers. However the pathologic similarities suggest that BRCA1 or associated pathways can become inactivated in triple-negative tumors via other mechanisms such as gene promoter methylation. We previously reported a positive association between oral contraceptive use and triple-negative breast cancer. Although we did not take into consideration the menopausal status of the patients the frequency of oral contraceptive use in our small cohort was found to be higher in patients with the triple-negative subtype compared with patients with other subtypes of breast cancer (35.3% vs 12.2%; P=.02). Taken together we propose that oral contraceptive use may be associated with an increased risk of developing triple-negative breast cancer. However to identify the exact role of oral contraceptive use in the development of breast cancer more preclinical and clinical studies are warranted. (full-text)

As part of an epidemiologic study of cancer of the large bowel in women, female residents of King and Pierce counties (Washington) who were diagnosed during 1976--77 were interviewed regarding previous gallbladder surgery. Their responses were compared with those of a random sample of women from the same population. A history of cholecystectomy was somewhat more frequent among patients with colon cancer than among controls--we estimate the colon cancer risk in women without a gallbladder to be 1.4 times that of other women--but the 05% confidence limits of the relative risk included 1.0 (0.8--2.5). There was no association between cholecystectomy and rectal cancer and, among the subsites of colon cancer, the magnitude of the excess risk failed to show any consistent right--left gradient. Nonepidemiologic data suggest that cholecystectomy could increase the risk of colon cancer. However, if such an association truly exists it is not a strong one, and studies larger than those conducted to date are needed to detect this association reliably.