Genetic testing for cancer risk has expanded rapidly. We examined clinical genetic testing and results among population-based patients with breast and ovarian cancer.
The study included all women 20 ...years of age or older diagnosed with breast or ovarian cancer in California and Georgia between 2013 and 2014 and reported to the SEER registries covering the entire state populations. SEER data were linked to results from four laboratories that performed nearly all germline cancer genetic testing. Testing use and results were analyzed at the gene level.
There were 77,085 patients with breast cancer and 6,001 with ovarian cancer. Nearly one quarter of those with breast cancer (24.1%) and one third of those with ovarian cancer (30.9%) had genetic test results. Among patients with ovarian cancer, testing was lower in blacks (21.6%; 95% CI, 18.1% to 25.4%;
whites, 33.8%; 95% CI, 32.3% to 35.3%) and uninsured patients (20.8%; 95% CI, 15.5% to 26.9%;
insured patients, 35.3%; 95% CI, 33.8% to 36.9%). Prevalent pathogenic variants in patients with breast cancer were
(3.2%),
(3.1%),
(1.6%),
(1.0%),
(0.7%), and
(0.4%); in patients with ovarian cancer, prevalent pathogenic variants were
(8.7%),
(5.8%),
(1.4%),
(0.9%),
(0.8%), and
(0.6%). Racial/ethnic differences in pathogenic variants included
(ovarian cancer: whites, 7.2%; 95% CI, 5.9% to 8.8%;
Hispanics, 16.1%; 95% CI, 11.8% to 21.2%) and
(breast cancer: whites, 2.3%; 95% CI, 1.8% to 2.8%;
blacks, 0.1%; 95% CI, 0% to 0.8%). When tested for all genes that current guidelines designate as associated with their cancer type, 7.8% of patients with breast cancer and 14.5% of patients with ovarian cancer had pathogenic variants.
Clinically-tested patients with breast and ovarian cancer in two large, diverse states had 8% to 15% prevalence of actionable pathogenic variants. Substantial testing gaps and disparities among patients with ovarian cancer are targets for improvement.
Abstract Purpose The United States (US) Food and Drug Administration and National Cancer Institute are seeking to improve methods to evaluate cancer as a clinical outcome in post-approval studies of ...drug and device safety. Challenges to monitoring cancer outcomes include years-long latency periods for many cancers, difficulty in tracking patients over long periods of time, missing outcomes of interest if relying upon reporting by patients or health care providers, burden of collecting high-quality, detailed documentation of incident cancers and low statistical power for rarer cancers. Methods Registration of incident cancers including patient identifiers occurs in every US state. Yet each state cancer registry is administered and must be accessed separately, which creates a nearly insurmountable burden of time, effort and cost for postmarket surveillance in multiple or all states. A voluntary process is in development which would allow states to reduce these barriers and enhance the health and safety of their residents. Called the Virtual Pooled Registry- Cancer Linkage System, state cancer registries will continue to hold and control their registry data while having access to a more streamlined process for postmarket surveillance, providing better quality, complete and more rapid discovery. Results A web based application and review process is in development with an additional effort devoted to highly automated linkage processes and federally compliant data file transmission security. Conclusions The Food and Drug Administration and National Cancer Institute will have enhanced abilities to perform high quality postmarket surveillance and other research at lower cost and with faster speed. This system also seeks to reduce cost and burden by participating state cancer registries. This process also supports the current modifications proposed by the US Department of Health and Human Services and 15 other Federal Departments and Agencies to modernize, strengthen and make more effective the Federal Policy for the Protection of Human Subjects known as the Common Rule.
Although it has been well-documented that obesity is associated with decreased risk of premenopausal breast cancer and increased risk of postmenopausal breast cancer, it is unclear whether these ...associations differ among breast cancer subtypes defined by the tumor protein expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).
We evaluated the associations of body mass index (BMI) at age 18 years and recent BMI in relation to risk of breast cancer overall and ER/PR/HER2-defined subtypes, in 6320 women (3934 case-patient participants, 2386 control participants) aged 35-64 years, who participated in one of three population-based case-control studies. We estimated multivariable-adjusted odd ratios (ORs) and corresponding 95% confidence intervals (CIs) using polychotomous unconditional logistic regression methods for case-control comparisons in premenopausal women and postmenopausal women.
BMI at age 18 years was inversely associated with risk of breast cancer, particularly among premenopausal women (≥ 25 vs. < 20 kg/m
, OR = 0.72, 95% CI = 0.53-0.96; per 5 kg/m
increase, OR = 0.83, 95% CI = 0.73-0.95). This inverse association did not differ across ER/PR/HER2-defined subtypes or by race (white women, African-American women). Recent BMI was not associated with risk of premenopausal breast cancer after adjustment for BMI at age 18 years; nevertheless, the analysis for the joint effects of BMI at age 18 years and recent BMI showed that premenopausal women in the highest categories of the two BMI measures (≥ 25 kg/m
at age 18 years and ≥ 30 kg/m
for recent BMI) had 46% lower risk of breast cancer than premenopausal women in the lowest categories of the two BMI measures (< 20 kg/m
at age 18 years and < 25 kg/m
for recent BMI; OR = 0.54, 95% CI = 0.38-0.78). Neither measure of BMI was statistically significantly associated with risk of postmenopausal breast cancer.
Our findings indicate that high BMI near the end of adolescence decreases risk of all ER/PR/HER2-defined subtypes of premenopausal breast cancer and also suggest that this benefit could be maximized among premenopausal women who consistently have high BMI during their premenopausal years.
Early age at menarche, nulliparity, late age at first completed pregnancy, and never having breastfed, are established breast cancer risk factors. However, among breast cancer subtypes, it remains ...unclear whether all of these are risk factors for triple-negative breast cancer (TNBC).
We evaluated the associations of these reproductive factors with TNBC, in 2658 patients with breast cancer (including 554 with TNBC) and 2448 controls aged 20-64 years, who participated in one of the three population-based case-control studies: the Women's Contraceptive and Reproductive Experiences Study, the Women's Breast Carcinoma in situ Study, or the Women's Learning the Influence of Family and Environment Study. We used multivariable polychotomous unconditional logistic regression methods to conduct case-control comparisons among breast cancer subtypes defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression status.
TNBC risk decreased with increasing duration of breastfeeding (P
= 0.006), but age at menarche, age at first completed pregnancy, and nulliparity were not associated with risk of TNBC. Parous women who breastfed for at least one year had a 31% lower risk of TNBC than parous women who had never breastfed (odds ratio, OR = 0.69; 95% confidence interval, CI = 0.50-0.96). The association between breastfeeding and risk of TNBC was modified by age and race. Parous African-American women aged 20-44 years who breastfed for 6 months or longer had an 82% lower risk of TNBC than their counterparts who had never breastfed (OR = 0.18, 95% CI = 0.07-0.46).
Our data indicate that breastfeeding decreases the risk of TNBC, especially for younger African-American women.
Although pregnancy-related factors such as nulliparity and late age at first full-term pregnancy are well-established risk factors for invasive breast cancer, the roles of these factors in the ...natural history of breast cancer development remain unclear.
Among 52,464 postmenopausal women participating in the California Teachers Study (CTS), 624 were diagnosed with breast carcinoma in situ (CIS) and 2,828 with invasive breast cancer between 1995 and 2007. Multivariable Cox proportional hazards regression methods were used to estimate relative risks associated with parity, age at first full-term pregnancy, breastfeeding, nausea or vomiting during pregnancy, and preeclampsia.
Compared with never-pregnant women, an increasing number of full-term pregnancies was associated with greater risk reduction for both breast CIS and invasive breast cancer (both P trend < 0.01). Women having four or more full-term pregnancies had a 31% lower breast CIS risk (RR = 0.69, 95% CI = 0.51 to 0.93) and 18% lower invasive breast cancer risk (RR = 0.82, 95% CI = 0.72 to 0.94). Parous women whose first full-term pregnancy occurred at age 35 years or later had a 118% greater risk for breast CIS (RR = 2.18, 95% CI = 1.36 to 3.49) and 27% greater risk for invasive breast cancer (RR = 1.27, 95% CI = 0.99 to 1.65) than those whose first full-term pregnancy occurred before age 21 years. Furthermore, parity was negatively associated with the risk of estrogen receptor-positive (ER+) or ER+/progesterone receptor-positive (PR+) while age at first full-term pregnancy was positively associated with the risk of ER+ or ER+/PR+ invasive breast cancer. Neither of these factors was statistically significantly associated with the risk of ER-negative (ER-) or ER-/PR- invasive breast cancer, tests for heterogeneity between subtypes did not reach statistical significance. No clear associations were detected for other pregnancy-related factors.
These results provide some epidemiologic evidence that parity and age at first full-term pregnancy are involved in the development of breast cancer among postmenopausal women. The role of these factors in risk of in situ versus invasive, and hormone receptor-positive versus -negative breast cancer merits further exploration.
On January 19, 2017, the United States federal government issued revisions to the Common Rule under which scientists who receive federal funding conduct research involving human subjects. The revised ...Common Rule expressly addresses public health surveillance in relation to scientific research and the protection of human subjects, and its impacts are anticipated to contribute to the efficiency of activities, including cancer registration and surveillance, and research that uses cancer registry data.
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