Rosner-Colditz model predicting breast cancer risk outperforms Gail in independent cohort.

Validation of breast cancer risk prediction models in an independent prospective data set is rare. We drew on prospective data from the Nurses’ Health Study and the California Teachers Study to validate the Rosner-Colditz breast cancer incidence model and compare it to the Gail model.1 (see report) The Rosner-Colditz model includes a range of established reproductive factors that are directly related to breast cancer risk, body mass index, and alcohol intake. 2 These are known causes of breast cancer. In particular, we include age at menopause and type of menopause (surgical or natural) – factors omitted from the Gail model. After aligning time periods for follow-up, we restricted populations to comparable age ranges (47 to 74), and followed them for incident invasive breast cancer (follow-up 1994 to 2008, Nurses’ Health Study [NHS]; and 1995 to 2009, California Teachers Study [CTS]). We identified 2026 cases during 540,617 person-years in NHS, and 1400 cases during 288,111 person-years in CTS.

To reflect application of a breast risk prediction model in clinical practice such as mammography screening services or primary care, we fit the Rosner–Colditz log incidence model and the Gail model using baseline data. We imputed future use of hormones based on type and prior duration of use and other covariates at the baseline. We assessed performance using area under the curve (AUC) and calibration methods. Participants in the CTS had fewer children, were leaner, consumed more alcohol, and were more frequent users of postmenopausal hormones. Incidence rate ratios for breast cancer showed significantly higher breast cancer in the CTS (IRR= 1.32, 95% CI 1.24 to 1.42). Parameters for the log-incidence model summarizing the relation for reproductive variables, history of benign breast disease, menopause and use of hormone therapy as well as alcohol, obesity, and family history, were comparable across the two cohorts. In the NHS the AUC was 0.60 (se 0.006) and applying the model to the CTS the performance in the independent data set (validation) was 0.586 (se 0.008). The Gail model gave values of 0.547 (se 0.008), a statistically significant 4% lower. For women 47 to 69, more typical of those for whom risk estimation would be indicated clinically, the AUC values for the log incidence model are 0.608 in NHS and 0.609 in CTS; and for Gail are 0.569 and 0.572. In both cohorts, performance of both models dropped off in older women 70 to 87.

We also assessed calibration – a measure of how well the model predicts incidence for a population. Calibration showed good estimation against SEER (used as a measure of US national incidence rates for breast cancer) with a non-significant 4% underestimate of overall breast cancer incidence when applying the model in the CTS population.


In sum, the Rosner-Colditz model performs consistently well when applied in an independent data set. Performance is stronger predicting incidence among women 47 to 69 and over a 5-year time interval. AUC values exceed those for Gail by 3 to 5% based on AUC when both are applied to the independent validation data set. Models may be further improved with addition of breast density or other markers of risk beyond the current model. Research in collaboration with the Breast Health Center is currently pursing these improvement.

Citations

1. Rosner, B.A. et al. Validation of Rosner-Colditz breast cancer incidence model using an independent data set, the California Teachers Study. Breast Cancer Res Treat (2013).


2. Colditz, G. & Rosner, B. Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the Nurses' Health Study. Am J Epidemiol 152, 950-64. (2000).

Reproductive risk factors drive risk of breast cancer in premenopausal women

To assess variation in the role of reproductive risk factors in relation to risk for breast cancer among premenopausal women we examined the relationship comparing women less than age 40 with older premenopausal women. Drawing on Data from the Nurses’ Health Studies, Dr. Warner and colleagues documented 374 incident cases of breast cancer diagnosed before age 40, and 2,533 cases diagnosed at age 40 and older among premenopausal women.1 Tumors in younger women were significantly more likely to be higher grade, larger size, and hormone receptor negative than were tumors in older premenopausal women. There was no significant difference according to age in associations between reproductive factors and risk of premenopausal breast cancer. For example, first birth at age 30 or older increased breast cancer risk in both age groups. Risk of premenopausal breast cancer decreased with each additional year of age at menarche in both age groups. As seen in postmenopausal women, among premenopausal parous women, breastfeeding was protective regardless of age at diagnosis.

The authors conclude that in the largest prospective examination of reproductive risk factors and risk of breast cancer before and after age 40, younger women were more likely to develop tumors with less favorable prognostic characteristics.

To learn more about how lifestyle can lower risk of premenopausal breast cancer read our earlier posts or go to 8IGHT WAYS to prevent breast cancer.

Citations

1. Warner, E.T. et al. Reproductive factors and risk of premenopausal breast cancer by age at diagnosis: Are there differences before and after age 40? Breast Cancer Res Treat (2013).

Breast cancer prevention should begin early in life

Breast cancer remains the second leading cause of cancer death among women. In the US it is estimated that 40,000 women will die from breast cancer in 2013. Just over 232,000 women will be diagnosed with breast cancer. Importantly, nearly a quarter of these new cases are diagnosed among women who are less than 50 years of age.

There are important successes with regard to detection and treatment of breast cancer. The rate of mortality has decreased by 30% over the last 20 years. The steady increase in incidence together with the aging population means that we have ever more total new cases of breast cancer diagnosed here and throughout the world.

Clearly, prevention is a much better choice than more diagnosis and treatment. It should be our first choice! We have the knowledge and tools to prevent more than half of breast cancer and avoid the pain and suffering that it causes. Prevention strategies will have the greatest impact when initiated early in life and sustained, but it is never too late for a woman to act.

Compelling scientific evidence shows that alcohol, obesity, and lack of exercise all cause breast cancer. Our recent posts here point to diet during adolescence and early adult years also offering important insights for prevention. Alcohol intake before first pregnancy increases risk of breast cancer throughout life. Further insights may help us understand how modifying other aspects of diet in this time frame could prevent the adverse effects of alcohol or reduce their impact on breast cancer risk.

Vegetable protein intake (including peanuts and peanut butter) show promise as does high soy intake through childhood and adolescence. We need to act on these findings now to bring prevention to women in their early adult years since much of breast cancer risk is set well before women enters menopause. We illustrate this in the figure below showing how reducing alcohol intake and sustained levels of physical activity from early life substantially reduce lifetime risk of breast cancer.

While higher levels of physical activity and weight loss after menopause can substantially reduce risk of breast cancer, we have not embarked on sustained population-wide efforts to increase physical activity and achieve sustained weight loss among middle aged women. Other strategies, such as selective estrogen receptor modulators (Tamoxifen and Raloxifene) are recommended to be considered by postmenopausal women at high risk. However, we should not wait till a quarter of breast cancers in a population of women have been diagnosed to think about starting prevention.

We have failed to harness our existing scientific knowledge to deliver effective prevention strategies. Its time to start!

See: 8IGHT WAYS to Prevent Breast Cancer

Preventing breast cancer: a diet with lots of fruits and vegetables

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Let's follow up on our recent post showing adolescent diet high in vegetable protein or nuts was associated with reduced risk of premalignant breast lesions in young adult women. (see previous post: Peanuts and lower risk of breast cancer)  This generated much interest and the potential of peanut butter to be of such major health benefit was noted by many. Of course peanuts are one of the leading sources of vegetable protein in modern US diets. We continue to explore ways to build on these findings to better inform prevention of the most common cancer diagnosed among women.

 A new report shows protection against breast cancer with diets that had higher intake of fruits and vegetables (a plant based diet) when consumed in midlife. The new report from the California Teachers Study followed 91,779 women for up to 14 years. 4140 women were diagnosed with invasive breast cancer.  A diet with higher plant based food intake gave significant reduction in risk of breast cancer. This study is consistent with the combined data from 20 prospective cohorts that included 993,466 women who were followed for 11 to 20 years and was published earlier this year (see paper). Over 24,000 cases of invasive breast cancer were diagnosed. Focusing on receptor status of the tumors, the investigators showed that higher intake of fruit and vegetables was related to lower risk of estrogen receptor negative breast cancer. Women in the top 20% of the population for intake of fruit and vegetables had a significant 18% reduction in risk of estrogen receptor negative breast cancer compared to the lowest 20% of the population.

Given we have fewer successful treatment options for estrogen receptor negative breast cancer the potential to prevent this subtype of disease becomes even more important.