Cannabis use is associated with patient and clinical factors in a population-based sample of colorectal cancer survivors.

PURPOSE: This study aimed to characterize patient and clinical factors associated with cannabis (marijuana) use among patients diagnosed with colorectal cancer (CRC). METHODS: We identified CRC patients, diagnosed from 2016 to 2018, using the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry. CRC patients were recruited via mail and telephone, and participants completed a questionnaire eliciting information on medical history, demographics, and lifestyle factors, including cannabis use. Cancer stage was obtained from SEER registry data. RESULTS: Of 1,433 survey respondents, 339 (24%) were current cannabis users. Current cannabis use was associated with younger age at diagnosis, lower BMI, and a higher prevalence of cigarette smoking and alcohol consumption (p-value < 0.05). Cannabis use was also associated with lower quality of life scores (FACT-C) and advanced-stage cancer (p-value < 0.05). CONCLUSION: Cannabis use among CRC patients was common. Patients with more advanced disease were more likely to report cannabis use. Use also varied by some personal factors, consistent with patterns in the general population. Given the high prevalence of cannabis use among CRC patients, research is needed to determine the benefits and harms of cannabis use for symptom management in cancer patients.

Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study.

Background: TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. Patients and methods: After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)-N0147 (NCT00079274) and PETACC3 (NCT00026273)-was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782). Results: TNM staging, MSI and BRAFV600E mutation status remained independent prognostic factors in multivariable models across clinical trials cohorts and observational studies. Concordance indices increased from 0.61-0.68 in the TNM alone model to 0.63-0.71 in models with added molecular markers, 0.65-0.73 with clinicopathological features and 0.66-0.74 with all covariates. In validation cohorts with complete annotation, the integrated time-dependent AUC rose from 0.64 for the TNM alone model to 0.67 for models that included clinicopathological features, with or without molecular markers. In patient cohorts that received adjuvant chemotherapy, the relative proportion of variance explained (R2) by TNM, clinicopathological features and molecular markers was on an average 65%, 25% and 10%, respectively. Conclusions: Incorporation of MSI, BRAFV600E and KRAS mutation status to overall survival models with TNM staging improves the ability to precisely prognosticate in stage II and III CC patients, but only modestly increases prediction accuracy in multivariable models that include clinicopathological features, particularly in chemotherapy-treated patients.

Characterisation of familial colorectal cancer Type X, Lynch syndrome, and non-familial colorectal cancer.

BACKGROUND: Familial Colorectal Cancer Type X (FCCTX) is defined as individuals with colorectal cancer (CRC) who families meet Amsterdam Criteria-1 (AC1), but whose tumours are DNA-mismatch-repair-proficient, unlike Lynch syndrome (LS). FCCTX does not have an increased risk of extra-colonic cancers. This analysis compares epidemiologic and clinicopathologic features among FCCTX, LS, and 'non-familial' (non-AC1) CRC cases. METHODS: From the Colon Cancer Family Registry, FCCTX (n=173), LS (n=303), and non-AC1 (n=9603) CRC cases were identified. Questionnaire-based epidemiologic information and CRC pathologic features were compared across case groups using polytomous logistic regression. RESULTS: Compared with LS, FCCTX cases were less likely to be current (vs never) smokers; have a proximal subsite (vs rectal) tumour; or have mucinous histology, poor differentiation, or tumour-infiltrating lymphocytes. There were no observed differences in co-morbidities or medication usage. CONCLUSIONS: FCCTX were less likely to be current tobacco users; other exposures were similar between these groups. Histopathologic differences highly suggestive of LS CRCs do not appear to be shared by FCCTX.

KRAS-mutation status in relation to colorectal cancer survival: the joint impact of correlated tumour markers.

BACKGROUND: Mutations in the Kirsten Ras (KRAS) oncogene are common in colorectal cancer (CRC). The role of KRAS-mutation status as a prognostic factor, however, is unclear. We evaluated the relationship between KRAS-mutation status and CRC survival, considering heterogeneity in this association by tumour and patient characteristics. METHODS: The population-based study included individuals diagnosed with CRC between 1998-2007 in Western Washington State. Tumour specimens were tested for KRAS exon 2 mutations, the BRAF p.V600E mutation, and microsatellite instability (MSI). We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between KRAS-mutation status and disease-specific and overall survival. Stratified analyses were conducted by age, sex, tumour site, stage, and MSI. We conducted additional analyses combining KRAS-mutation, BRAF-mutation, and MSI status. RESULTS: Among 1989 cases, 31% had KRAS-mutated CRC. Kirsten Ras (KRAS)-mutated CRC was associated with poorer disease-specific survival (HR=1.37, 95% CI: 1.13-1.66). This association was not evident in cases who presented with distant-stage CRC. Cases with KRAS-wild-type/BRAF-wild-type/MSI-high CRC had the most favourable prognosis; those with CRC exhibiting a KRAS- or BRAF-mutation and no MSI had the poorest prognosis. Patterns were similar for overall survival. CONCLUSION: Kirsten Ras (KRAS)-mutated CRC was associated with statistically significantly poorer survival after diagnosis than KRAS-wild-type CRC.

Pre-diagnostic NSAID use but not hormone therapy is associated with improved colorectal cancer survival in women.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) and hormone therapy (HT) independently decrease the risk of colorectal cancer. However, their role in altering survival after a colorectal cancer diagnosis is not well established. METHODS: We examined the association between the use of these common medications before diagnosis and colorectal cancer survival among women in western Washington State diagnosed with incident colorectal cancer from 1997 to 2002. Cases were ascertained using the Surveillance, Epidemiology and End Results cancer registry; mortality follow-up was completed through linkages to the National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We observed no overall association between colorectal cancer survival and pre-diagnostic NSAID use. However, when stratified by tumour sub-site, NSAID use was associated with a reduced risk of colorectal cancer mortality for women diagnosed with proximal (HR=0.55; 95% CI: 0.32-0.92), but not distal or rectal (HR=1.32; 95% CI: 0.83-2.10) tumours. The usage of HT was not associated with colorectal cancer survival overall or by tumour sub-site. CONCLUSION: Usage of NSAIDs before diagnosis may be associated with improved colorectal cancer survival among women diagnosed with proximal tumours. The usage of HT does not appear to have a function in altering colorectal cancer mortality.

Body mass index in early adulthood and colorectal cancer risk for carriers and non-carriers of germline mutations in DNA mismatch repair genes.

BACKGROUND: Carriers of germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), but the modifiers of this risk are not well established. We estimated an association between body mass index (BMI) in early adulthood and subsequent risk of CRC for carriers and, as a comparison, estimated the association for non-carriers. METHODS: A weighted Cox regression was used to analyse height and weight at 20 years reported by 1324 carriers of MMR gene mutations (500 MLH1, 648 MSH2, 117 MSH6 and 59 PMS2) and 1219 non-carriers from the Colon Cancer Family Registry. RESULTS: During 122,304 person-years of observation, we observed diagnoses of CRC for 659 carriers (50%) and 36 non-carriers (3%). For carriers, the risk of CRC increased by 30% for each 5 kg m(-2) increment in BMI in early adulthood (hazard ratio, HR: 1.30; 95% confidence interval, CI: 1.08-1.58; P=0.01), and increased by 64% for non-carriers (HR: 1.64; 95% CI: 1.02-2.64; P=0.04) after adjusting for sex, country, cigarette smoking and alcohol drinking (and the MMR gene that was mutated in carriers). The difference in HRs for carriers and non-carriers was not statistically significant (P=0.50). For MLH1 and PMS2 (MutLα heterodimer) mutation carriers combined, the corresponding increase was 36% (HR: 1.36; 95% CI: 1.05-1.76; P=0.02). For MSH2 and MSH6 (MutSα heterodimer) mutation carriers combined, the HR was 1.26 (95% CI: 0.96-1.65; P=0.09). There was no significant difference between the HRs for MutLα and MutSα heterodimer carriers (P=0.56). CONCLUSION: Body mass index in early adulthood is positively associated with risk of CRC for MMR gene mutation carriers and non-carriers.

Reproductive factors and histologic subtype in relation to mortality after a breast cancer diagnosis.

Evidence suggests that certain reproductive factors are more strongly associated with the incidence of lobular than of ductal breast cancer. The mechanisms influencing breast cancer incidence histology may also affect survival. Women with invasive breast cancer (N = 22,302) diagnosed during 1986-2005 were enrolled in a series of population-based studies in three US states. Participants completed telephone interviews regarding reproductive exposures and other breast cancer risk factors. Histologic subtype was obtained from state cancer registries. Vital status and cause of death were determined through December 2006 using the National Death Index. Women were followed for 9.8 years on average with 3,050 breast cancer deaths documented. Adjusted hazard rate ratios (HR) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazards regression models for breast cancer-specific and all-cause mortality. Parity was inversely associated with breast cancer-specific mortality (P (Trend) = 0.002). Associations were similar though attenuated for all-cause mortality. In women diagnosed with ductal breast cancer, a 15% reduction in breast cancer-specific mortality was observed in women with five or more children when compared to those with no children (HR = 0.85, 95% CI: 0.73-1.00). A similar inverse though non-significant association was observed in women with lobular subtype (HR = 0.70, 95% CI: 0.43-1.14). The trend did not extend to mixed ductal-lobular breast cancer. Age at first birth had no consistent relationship with breast cancer-specific or all-cause mortality. We found increasing parity reduced mortality in ductal and lobular breast cancer. The number of full-term births, rather than age at first birth, has an effect on both breast cancer-specific and overall mortality.

Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk.

BACKGROUND: Bisphosphanates are used primarily for the prevention and treatment of osteoporosis, and are also indicated for osseous complications of malignancy. In addition to their bone resorption properties, the most commonly used nitrogen-containing bisphosphonate compounds also inhibit protein prenylation, and thus may exert anti-tumour properties. METHODS: To evaluate whether the use of these drugs may be associated with cancer, specifically breast cancer, we conducted a population-based case-control study in Wisconsin from 2003 to 2006. Participants included 2936 incident invasive breast cancer cases and 2975 population controls aged < 70 years. Bisphosphonate use and potential confounders were assessed by interview. RESULTS: Using multivariable logistic regression, the odds ratio for breast cancer in current bisphosphonate users compared with non-users was 0.67 (95% confidence interval 0.51-0.89). Increasing duration of use was associated with a greater reduction in risk (P-trend=0.01). Risk reduction was observed in women who were not obese (P-interaction=0.005). CONCLUSION: These results are suggestive of an additional benefit of the common use of bisphosphonates, in this instance, the reduction in breast cancer risk.

Inverse association of NSAID use and ovarian cancer in relation to oral contraceptive use and parity.

We examined the association between non-steroidal anti-inflammatory drug (NSAID) use and ovarian cancer by potential effect modifiers, parity and oral contraceptive use, in a population-based case-control study conducted in Wisconsin and Massachusetts. Women reported prior use of NSAIDs and information on risk factors in a telephone interview. A total of 487 invasive ovarian cancer cases and 2653 control women aged 20-74 years were included in the analysis. After adjustment for age, state of residence and other covariates, ever use of NSAIDs was inversely associated with ovarian cancer in never users of oral contraceptives (odds ratio (OR)=0.58, 95% confidence interval (CI) 0.42-0.80) but not for ever users (OR=0.98, 95% CI 0.71-1.35) (P-interaction=0.03). A reduced risk with NSAID use was also noted in nulliparous women (OR=0.47, 95% CI 0.27-0.82) but not among parous women (OR=0.81, 95% CI 0.64-1.04) (P-interaction=0.05). These results suggest that use of NSAIDs were beneficial to women at greatest risk for ovarian cancer.

Urinary cadmium levels and tobacco smoke exposure in women age 20-69 years in the United States.

Cadmium is a toxic, bioaccumulated heavy metal with a half-life of one to four decades in humans (CDC, 2005). Primary exposure sources include food and tobacco smoke. In our population-based study, a risk-factor interview was conducted as part of a breast cancer study for 251 randomly selected women living in Wisconsin (USA), aged 20-69 yr, and spot-urine specimens were also obtained. Urine collection kits were carefully designed to minimize trace element contamination during specimen collection and handling in each participant's home. Urine cadmium concentrations were quantified using inductively coupled plasma-mass spectrometry, and creatinine levels and specific gravity were also determined. Statistically significant increasing creatinine-adjusted urinary cadmium mean levels relative to smoking status (never, former, and current respectively) were observed. A difference in mean cadmium levels for nonsmokers who reported environmental tobacco smoke exposure during childhood or the recent past (approximately 2 yr prior to the interview) for exposure at home, at work, or in social settings compared to those who reported no exposure was not found.

Weight change and risk of endometrial cancer.

BACKGROUND: Obesity is an established risk factor for endometrial cancer. Less well understood is the role of weight gain and weight change in determining risk. METHODS: We analysed data from a population-based case-control study to evaluate the associations of body mass index (BMI), weight gain, and weight cycling with risk of endometrial cancer. Cases (n=740) under age 80 with a new diagnosis of endometrial cancer were identified from Wisconsin's cancer registry. Controls (n=2342) were randomly selected from driver's license lists and Medicare beneficiary files. Body size at three time points and other risk factor information were ascertained by interview in 1992-95. RESULTS: Endometrial cases were more likely than controls to be nulliparous, have early ages at menarche and late ages at menopause, be diabetic, smoke cigarettes, and use post-menopausal hormones. After adjustment for these factors, increasing BMI was associated with increased risk (P-trend<0.001); women in the top quartile of BMI (>29 kg/m2) had a 3-fold greater risk of endometrial cancer [95% confidence interval (95% CI) 2.4-4.2] compared with women in the lowest quartile (<23 kg/-m2). For each 5 kg weight gain, the odds ratio (OR) for endometrial cancer risk equalled 1.2 (95% CI 1.2-1.3). History of weight cycling modestly increased risk after adjustment for BMI and other factors (OR=1.3; 95% CI 1.0-1.6). In addition, women who reported sustained weight loss had a reduced risk of endometrial cancer (OR=0.7; 95% CI 0.6-0.9). CONCLUSIONS: These results suggest that weight gain and lack of weight stability are associated with risk of endometrial cancer.

Postmenopausal hormone use and risk of large-bowel cancer.

BACKGROUND: The epidemiology of large-bowel cancer suggests a role for endocrine factors in its development. Although analytic studies have not consistently provided evidence for an association between reproductive history and large-bowel cancer, some relatively small studies have observed a reduced risk among women using postmenopausal hormone replacement therapy (HRT). PURPOSE: This study was planned to evaluate more precisely the relationship between HRT and the risk of colon and rectal cancers. METHODS: Female residents of Wisconsin aged 30-74 years with a diagnosis of colon or rectal cancer within 2 years were identified through a statewide tumor registry. Control subjects were randomly selected from lists of licensed drivers if the case subjects were less than 65 years old and from lists of Medicare beneficiaries if they were 65-74 years old. Information on post-menopausal hormone replacement use, medical history, and family history was obtained in telephone interviews. After premenopausal women were excluded, 694 case subjects and 1622 control subjects remained for analysis. The odds ratios and 95% confidence intervals (CIs) obtained from conditional logistic regression models were used to estimate relative risks (RRs). All RRs were adjusted for age, family history of large-bowel cancer, use of screening sigmoidoscopy, and recent alcohol consumption. RESULTS: Compared with postmenopausal women who never used HRT, recent users had an RR of 0.54 (95% CI = 0.36-0.81) for colon cancer and an RR of 0.91 (95% CI = 0.54-1.55) for rectal cancer. This inverse association was observed among users of both estrogen only and combined estrogen and progestin preparations. Decreasing time since last use was inversely associated with colon cancer risk (P for trend < .001). The effect of HRT appeared to be stronger among women at lower absolute risk of colon cancer, particularly among women with lean body mass. CONCLUSIONS: Use of HRT was associated with a statistically significant reduced risk of colon cancer. In contrast, no statistically significant relationship was observed for rectal cancer. Given the widespread use of postmenopausal hormones and the morbidity and mortality from adenocarcinoma of the bowel in women, these findings may have potentially important public health implications.

Cancer treatment and age: patient perspectives.

BACKGROUND: Despite some evidence that age does not meaningfully influence the efficacy or toxicity of cancer treatment, older patients tend to receive less comprehensive cancer therapies. PURPOSE: We conducted a population-based study to evaluate the selection of cancer treatment among the elderly. METHODS: Between September 1 and November 30, 1990, we interviewed by telephone a sample of 628 female Wisconsin residents recently diagnosed with breast (507) or colorectal (121) cancer. The women, aged 20-74 at the time of diagnosis, were identified through Wisconsin's statewide tumor registry. The approximately 30-minute long telephone interview, part of a larger study of cancer etiology, included questions on treatment history, physician specialty, and reasons for the selection of specific therapies. Analyses compared the proportion of subjects with various treatment characteristics according to age (< 65 and > or = 65 years). In evaluating the effect of age on selected therapies, we adjusted summary proportions for stage of disease using the indirect method. The Mantel-Haenszel chi square statistic was used to evaluate statistical significance of the differences in proportions. RESULTS: After adjusting for stage of disease at diagnosis, substantial variation was observed in cancer treatment according to age for both breast and colorectal cancer. Older women (> or = 65 years) with breast cancer were less likely than younger women (< 65 years) to have received conservative surgery, radiation, and adjuvant therapy. Older women were, in fact, more likely than younger women to accept mastectomy (P = .03). Consultation with a medical or radiation oncologist was less common among older than younger patients (57% versus 73%). Older women were also less likely to have alternative therapies presented to them (19% versus 31%). While older patients were less likely to have been offered adjuvant treatments, like chemotherapy (P < .01), they were also more likely than younger women to reject these treatments when offered (P = .01). These differences were observed in both breast and colorectal cancer patients. Regardless of age, the most common reasons for not selecting treatments were physicians' recommendations and the desire for more comprehensive treatment. Concern about side effects, however, was more frequently reported by older women (P = .07). CONCLUSION AND IMPLICATION: Patients' ages influence the choice of treatment. Physicians offer older women with cancer different treatments from those offered to younger women and are less likely to recommend specialist consultation. Physicians' advice and description of toxicity may influence patients' selection of treatment. However, older patients' concerns about the consequences of cancer treatment may also influence treatment choice.

Incidence of vulvar carcinoma in relation to menstrual, reproductive, and medical factors.

Fifty-seven female residents of King and Pierce Counties (Washington State) with a new diagnosis of in situ or invasive vulvar carcinoma during 1976-79 were interviewed concerning their menstrual, reproductive, and medical histories. A random sample of women residing in the same area was interviewed for comparison. A greater proportion of women with in situ vulvar tumors than control subjects were of low educational level, reported a history of oral contraceptive use, experienced early age at first birth, late age at menopause, and were current or former cigarette smokers. Menstrual and reproductive factors were similar between women with invasive vulvar cancer and controls, but a greater proportion of cases reported a history of diabetes and of cigarette smoking. The factors found in this study to be associated with in situ vulvar carcinoma are similar to those observed among women with cervical cancer. In addition, since the vulva and cervix both are derived from cloacal tissue, and neoplasms of the two sites occur together more often than would be expected by chance, in situ vulvar and cervical tumors may share some common etiologies.

Mammography screening and increased incidence of breast cancer in Wisconsin.

The age-adjusted incidence of breast cancer among Wisconsin women age 40 and older has increased by almost one third since the early 1980s. To estimate what portion of the observed increase in breast cancer incidence is due to mammography screening, we developed a model of the lead-time effect of this screening test and its impact on incidence. The model incorporates annual age-specific information including 1) the expected number of cases, 2) the rate of screening, 3) the detection ratio of screening mammography, and 4) the lead time of screening mammography. For women 40 years of age and older, the model predicts a 25% increase in incidence, compared with an observed increase of 28%. Overall, mammography screening explains 74% of the difference between the expected and observed number of cases over the study period. A greater portion of the increase in incidence among postmenopausal women is attributed to mammography screening than among younger women. The increase in the use of mammography appears to account for most but not all of the increased incidence of breast cancer in Wisconsin.

Breast self-examination in relation to the occurrence of advanced breast cancer.

Two hundred nine female enrollees of the Group Health Cooperative of Puget Sound who developed advanced-stage breast cancer during the period 1982-1988 were interviewed about their practice of breast self-examination (BSE), use of other breast cancer screening modalities, and medical and reproductive histories. Each subject's description of how she performed the examination was scored according to her mention of up to 10 recommended BSE techniques. A random sample of 433 women without advanced-stage breast cancer from the same population was interviewed for comparison. Relative to women not practicing BSE, the risk of advanced-stage breast cancer among BSE users was 1.15 (95% confidence interval, 0.73-1.81). Frequency of BSE did not differ between women with advanced-stage breast cancer and control subjects, whether in all subjects or in subgroups defined by age, use of mammography, or frequency of clinical breast examinations. While self-described proficiency in BSE was generally low in both case and control subjects, the small percentage of women reporting more thorough self-examinations, regardless of frequency, had about a 35% decrease in the occurrence of advanced-stage breast cancer compared to women who did not perform BSE. These results suggest that, while carefully performed BSE may avoid the development of some advanced-stage breast cancers, BSE as practiced by most Seattle-area women is of little or no benefit.

Screening sigmoidoscopy and colorectal cancer mortality.

BACKGROUND: Sigmoidoscopy may reduce colorectal cancer mortality by identifying both cancers and precursor lesions (including polyps) for treatment; however, evidence regarding the efficacy of this technique as a screening procedure is extremely limited. PURPOSE: In the absence of data from randomized controlled trials, we performed a retrospective case-control study to determine if sigmoidoscopy screening is associated with a reduction in colorectal cancer mortality. METHODS: The medical records of 66 members of the Greater Marshfield Community Health Plan (GMCHP) who died of large-bowel cancer from 1979 to 1988 were reviewed for history of screening for colorectal cancer (case subjects). For comparison, the records of 196 GMCHP members of similar gender, age, and enrollment duration were randomly selected for review (control subjects). RESULTS: History of screening sigmoidoscopy was much less common among case subjects (10%) than among control subjects (30%). Risk for death from colorectal cancer was reduced among individuals having had a single examination by screening sigmoidoscopy (odds ratio = 0.21; 95% confidence interval = 0.08-0.52), compared with the risk for those who never had one. The reduction in risk appeared to be limited to tumors in the rectum and distal colon. Neither fecal occult blood testing nor digital rectal examination was associated with a reduction in colorectal cancer mortality. CONCLUSIONS: These results suggest that screening sigmoidoscopy can substantially reduce mortality from cancers of the rectum and distal colon.

Effects of tamoxifen on cardiovascular risk factors in postmenopausal women after 5 years of treatment.

BACKGROUND: Adjuvant tamoxifen therapy for breast cancer has been given for a period of several years. Cardiovascular diseases increased in incidence rapidly in women older than 60 years. Favorable changes in cardiovascular risk factors have been seen with 2 years of tamoxifen therapy, and lower rates of myocardial infarction and of hospitalization for heart disease have been observed in tamoxifen-treated women. PURPOSE: We sought to evaluate changes in risk factors for cardiovascular diseases in postmenopausal women after therapy with tamoxifen for 5 years. METHODS: Five years after their initial entry in a 2-year randomized, placebo-controlled toxicity study, we re-examined 62 of the original 140 disease-free, axillary node-negative postmenopausal breast cancer patients. These 62 patients were women available for study because they had not suffered major illness and had continued on either the tamoxifen or no-tamoxifen regimen to which they had been originally randomly assigned for the entire 5 years. Patient and control blood samples were analyzed for total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and subfractions, triglycerides, apolipoprotein AI, apolipoprotein B, lipoprotein(a), fibrinogen, glucose, and platelets. RESULTS: At base line for all measurements except atherogenic lipoprotein [lipoprotein(a)], the 30 long-term tamoxifen recipients and the 32 long-term no-tamoxifen recipients were not significantly different. After 5 years, levels of total serum cholesterol (P < .001), LDL cholesterol (P < .001), and lipoprotein(a) (P = .001) were significantly lower, and apolipoprotein AI levels were significantly higher (P < .001) in the tamoxifen-treated group compared with the no-tamoxifen group. Apolipoprotein B levels increased to a greater extent in the no-tamoxifen than in the tamoxifen group (P < .001). After 5 years, fibrinogen level decrease and triglyceride level increases in the tamoxifen group compared with the no-tamoxifen group were of borderline statistical significance and HDL cholesterol levels were not different in the two groups. CONCLUSION: Favorable changes in lipid, lipoprotein, and fibrinogen levels seen early in tamoxifen therapy in postmenopausal women persist with treatment of 5 years. IMPLICATIONS: The types and magnitude of changes in cardiovascular risk factors seen here with tamoxifen are similar to a certain extent with those seen with estrogen supplements. Further risk-factor and ethnic-group data are needed to estimate the magnitude of expected benefits of tamoxifen treatment on incidence of heart disease.

Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer.

We conducted a 2-year, randomized, double-blind, placebo-controlled toxicity trial of therapy with tamoxifen (10 mg twice a day) in 140 postmenopausal women with a history of breast cancer and histologically negative axillary lymph nodes. These women had been treated with surgery with or without radiotherapy. At a 3-month evaluation, tamoxifen-treated women showed a significant decrease in fasting plasma levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, which persisted at 6- and 12-month evaluations. During the first 12 months, plasma triglyceride levels increased; small but significant decreases in high-density lipoprotein cholesterol (HDL) were observed in tamoxifen-treated women, but ratios of total cholesterol to HDL cholesterol and of LDL to HDL cholesterol changed favorably. While data relating lipid/lipoprotein profiles and cardiovascular disease are limited in women, current evidence suggests that total cholesterol and possibly low-density lipoprotein cholesterol are risk factors. We conclude that during the first 12 months of treatment, tamoxifen exerts a favorable effect on the lipid profile in postmenopausal women with early stage breast cancer.