Box 1.

Summary and research recommendations from the National Cancer Institute workshop “Postpartum Breast Remodeling, Lactation, and Breast Cancer Risk: Towards Improved Risk Assessment and Prevention”

Summary of Research Presented

1. In the general population, long durations of lactation are associated with a small reduction in overall breast cancer risk, in addition to many other health benefits for mother and child.

2. Breastfeeding may provide greater protection against triple-negative, basal-like, and BRCA1 mutation–associated breast cancer, suggesting particular protection against aggressive types of tumors.

3. In humans, effects of parity and lactation on breast cancer risk are largely inseparable.

4. First pregnancy induces hormonal changes, some of which persist long-term. It is unclear how lactation affects the long-term hormonal environment over and above that of pregnancy.

5. Data from animal models demonstrate a molecular “involution signature” regulated by Stat3 signaling.

6. Recent pregnancy may increase near-term risk of breast cancer and poor prognosis. In the rodent model, involution of the mammary gland demonstrates shared characteristics with wound healing and promotes tumorigenesis. Nonsteroidal anti-inflammatory drugs can inhibit tumorigenesis induced by involution in this model.

7. Aspects of the research in rodent models may be applicable to human breast remodeling postweaning; however, the rodent mammary gland differs in composition and organization from the human breast. The degree to which involution induces inflammation may also vary across animal models and from animal to human but may be modifiable.

8. Multiple components of milk can be assessed and vary with both physiological and pathological states (eg, weaning, inflammation, infection). These include hormones, cytokines, glycoproteins, and methylation of epithelial cells found in milk. Association of these markers with breast cancer risk is yet to be determined.

Recommendations for Future Research

1. Examine datasets to determine associations between parity, lactation, and breast cancer risk and outcomes, including studies of women who are BRCA1 mutation carriers and assessment of relationships by molecular subtype.

2. Refine analyses of lactation by collecting more detailed data (eg, duration per child, period of exclusive breastfeeding, weaning strategy/duration).

3. Use animal models to try to separate effects of parity and lactation.

4. Use animal models to examine the role of involution in promoting different breast cancer subtypes and the mechanisms and markers related to these processes.

5. Determine association of parity and lactation with long-term physiological states (eg, hormones, breast stem cells, breast microenvironment).

6. Conduct methods studies that explore collection, storage, and variability (within a woman over time and between women) of milk samples with regard to different markers in milk (eg, hormones, glycoproteins, cytokines, epithelial cells).

7. Examine associations of soluble or cellular components in milk with markers of breast cancer risk (eg, mammographic density).