Marion M. Lee

Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors

IntroductionThe aim of this study was to describe breast tumor subtypes by common breast cancer risk factors and to determine correlates of subtypes using baseline data from two pooled prospective breast cancer studies within a large health maintenance organization.MethodsTumor data on 2544 invasive breast cancer cases subtyped by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (Her2) status were obtained (1868 luminal A tumors, 294 luminal B tumors, 288 triple-negative tumors and 94 Her2-overexpressing tumors). Demographic, reproductive and lifestyle information was collected either in person or by mailed questionnaires. Case-only odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age at diagnosis, race/ethnicity, and study origin.ResultsCompared with luminal A cases, luminal B cases were more likely to be younger at diagnosis (P = 0.0001) and were less likely to consume alcohol (OR = 0.74, 95% CI = 0.56 to 0.98), use hormone replacement therapy (HRT) (OR = 0.66, 95% CI = 0.46 to 0.94), and oral contraceptives (OR = 0.73, 95% CI = 0.55 to 0.96). Compared with luminal A cases, triple-negative cases tended to be younger at diagnosis (P ≤ 0.0001) and African American (OR = 3.14, 95% CI = 2.12 to 4.16), were more likely to have not breastfed if they had parity greater than or equal to three (OR = 1.68, 95% CI = 1.00 to 2.81), and were more likely to be overweight (OR = 1.82, 95% CI = 1.03 to 3.24) or obese (OR = 1.97, 95% CI = 1.03 to 3.77) if premenopausal. Her2-overexpressing cases were more likely to be younger at diagnosis (P = 0.03) and Hispanic (OR = 2.19, 95% CI = 1.16 to 4.13) or Asian (OR = 2.02, 95% CI = 1.05 to 3.88), and less likely to use HRT (OR = 0.45, 95% CI = 0.26 to 0.79).ConclusionsThese observations suggest that investigators should consider tumor heterogeneity in associations with traditional breast cancer risk factors. Important modifiable lifestyle factors that may be related to the development of a specific tumor subtype, but not all subtypes, include obesity, breastfeeding, and alcohol consumption. Future work that will further categorize triple-negative cases into basal and non-basal tumors may help to elucidate these associations further.

Risk factors for breast cancer in a population with high incidence rates

BackgroundThis report examines generally recognized breast cancer risk factors and years of residence in Marin County, California, an area with high breast cancer incidence and mortality rates.MethodsEligible women who were residents of Marin County diagnosed with breast cancer in 1997–99 and women without breast cancer obtained through random digit dialing, frequency-matched by cases age at diagnosis and ethnicity, participated in either full in-person or abbreviated telephone interviews.ResultsIn multivariate analyses, 285 cases were statistically significantly more likely than 286 controls to report being premenopausal, never to have used birth control pills, a lower highest lifetime body mass index, four or more mammograms in 1990–94, beginning drinking after the age of 21, on average drinking two or more drinks per day, the highest quartile of pack-years of cigarette smoking and having been raised in an organized religion. Cases and controls did not significantly differ with regard to having a first-degree relative with breast cancer, a history of benign breast biopsy, previous radiation treatment, age at menarche, parity, use of hormone replacement therapy, age of first living in Marin County, or total years lived in Marin County. Results for several factors differed for women aged under 50 years or 50 years and over.ConclusionsDespite similar distributions of several known breast cancer risk factors, case-control differences in alcohol consumption suggest that risk in this high-risk population might be modifiable. Intensive study of this or other areas of similarly high incidence might reveal other important risk factors proximate to diagnosis.

The Pathways Study: a prospective study of breast cancer survivorship within Kaiser Permanente Northern California

ObjectiveWith 2.3xa0million breast cancer survivors in the US today, identification of modifiable factors associated with breast cancer recurrence and survival is increasingly important. Only recently new studies have been designed to examine the impact of lifestyle factors on prognosis, including Pathways, a prospective study of women with breast cancer in Kaiser Permanente Northern California (KPNC).MethodsPathways aims to examine the effect on recurrence and survival of (1) lifestyle factors such as diet, physical activity, quality of life, and use of alternative therapies and (2) molecular factors such as genetic polymorphisms involved in metabolism of chemotherapeutic agents. Eligibility includes any woman diagnosed with invasive breast cancer within KPNC, no previous diagnosis of other invasive cancer, age 21xa0years or older, and ability to speak English, Spanish, Cantonese, or Mandarin. Newly diagnosed patients are identified daily from electronic pathology records and are enrolled within two months of diagnosis. An extensive baseline interview is conducted, blood and saliva samples are collected, and body measurements are taken. Women are followed for lifestyle updates, treatment, and outcomes by self-report and query of KPNC databases.ResultsRecruitment began in 9 January, 2006, and as of 16 January, 2008, 1,539 women have been enrolled along with collection of 1,323 blood samples (86%) and 1,398 saliva samples (91%).ConclusionsThe Pathways Study will become a rich resource to examine behavioral and molecular factors and breast cancer prognosis.

Dietary assessment in the California Teachers Study: reproducibility and validity

ObjectiveTo evaluate the reproducibility and validity of the food-frequency questionnaire (FFQ) used in the California Teachers Study (CTS) cohort and to use this data to quantify the effects of correcting nutrient-breast cancer relative risks for measurement error.MethodsOne hundred and ninety five CTS cohort members participated in a 10-month dietary validation study that included four 24-h dietary recalls and pre- and post-study FFQs. Shrout–Fleiss intraclass correlations for reproducibility were computed. Under several standard assumptions concerning the correlations of errors in the FFQs and 24-h recalls, we calculated energy-adjusted deattenuated Pearson correlations for validity and tested for differences in validity according to a number of demographic and other risk factors. For each nutrient, we compared the performance of the FFQ versus the 24-h recalls, estimating the number of days of recalls that give equivalent information about true intake as does a single FFQ. Finally, the effects of adjustment for measurement error on risk estimates were evaluated in 44,423 postmenopausal cohort members, 1,544 of whom developed breast cancer during seven years of follow-up. Relative risks (RR) and confidence intervals (CI) were calculated using Cox proportional hazards with and without correction for measurement error.ResultsReproducibility correlations for the nutrients ranged from 0.60 to 0.87. With a few exceptions, validity correlations were reasonably high (range: 0.55–0.85), including rxa0=xa00.74 for alcohol. Performance of the FFQ differed by age for percent of calories from fat and by body mass index and hormone therapy use for alcohol consumption. For most nutrients examined, our FFQ is comparable to two to six recalls for each subject in capturing true intake. In the measurement error-adjusted risk analyses, corrected RRs were within 13% of uncorrected values for all nutrients examined except for linoleic acid. For alcohol consumption the corrected RR (per 20xa0g/1,000xa0kcal/d) was 1.36 (95% CI: 1.03–1.51) compared to the uncorrected estimate of 1.25 (95% CI: 1.10–1.42).ConclusionThe FFQ dietary assessment used in the CTS is reproducible and valid for all nutrients except the unsaturated fatty acids. Correcting relative risk estimates for measurement error resulted in relatively small changes in the associations between the majority of nutrients and the risk of postmenopausal breast cancer.

Patient-physician interaction and quality of life in recently diagnosed breast cancer patients.

Few studies have explored how patient–physician interactions influence patients’ quality of life (QOL). In a prospective cohort study of 1,855 women diagnosed with invasive breast cancer in the Kaiser Permanente Northern California Medical Care Program from 2006 to 2011, we examined associations between patient–physician interactions during cancer treatment and QOL, overall and by racial/ethnic group. Participants completed the interpersonal processes of care (IPC) survey at approximately 8xa0months post-diagnosis to assess specific domains of the patient–physician interaction during the months after cancer diagnosis. Domains included: compassion, elicited concerns, explained results, decided together, lack of clarity, discrimination due to race/ethnicity, and disrespectful office staff. The functional assessment of cancer therapy-breast cancer was completed concurrently to measure QOL. Linear regression models examined the association of IPC with QOL, first adjusting for patient covariates including age, race, clinical factors, and psychosocial measures and then for physician characteristics such as age, sex, race/ethnicity, and specialty. For all participants (nxa0=xa01,855), IPC scores suggesting greater lack of clarity, discrimination due to race/ethnicity, and disrespectful office staff in patient–physician interactions were associated with lower QOL (P<xa00.01). IPC scores suggesting physicians demonstrating compassion, eliciting concerns, or explaining results were associated with higher QOL (P<xa00.01). Among Whites (nxa0=xa01,306), only the associations with higher QOL remained. African Americans (nxa0=xa0110) who reported higher scores on physician compassion and elicited concerns had higher QOL, whereas higher scores for disrespectful office staff had lower QOL. No associations were observed among Asians (nxa0=xa0201) and Hispanics (nxa0=xa0186). After further adjustment for physician factors, the associations among Whites remained, whereas those among African Americans disappeared. In the breast cancer treatment setting, characteristics of the patient–physician interaction as perceived by the patient are associated with QOL, yet were not specific to patient race/ethnicity.