Study: Improving outcomes for young women with breast cancer: fertility and childbearing issues

IN-DEPTH REVIEW OF RESEARCH
Breast Cancer in Young women

Many studies have indicated that compared to older breast cancer survivors, young survivors tend to have:

• worse rates of survival (SEER 2010-2015).
• worse quality of life (Kroenke et al.2004).

In studies by Ganz, et al. (2003) and Howard-Anderson, et al. (2012), compared to older patients, young premenopausal women (25-51 years old at diagnosis) have:

• better physical function
• worse social and emotion function
• more depression and mental health challenges
• unique issues, including fertility, sexual health, parenting, partnering and facing the possibility of mortality at a young age

Researchers of this study wanted to know:

This study is designed to evaluate the biological, medical and psychosocial outcomes for young women diagnosed with breast cancer. The goal is to understand the underlying reasons for differences in outcomes for young women with breast cancer and how to address those differences.

Populations looked at in this study:

The Young Women's Breast Cancer Study included 1,302 women who were 40 years old or younger and diagnosed with breast cancer between 2006 and 2016. The median age of participants was 37. Researchers reviewed the pathology of tumor samples to confirm diagnosis as well as other medical records. Participants were surveyed every 6 months for 3 years and then annually thereafter.

Study findings:  

Compared to the general population of women with breast cancer, the population of young women with breast cancer have more of a diverse mix of tumor types. Young breast cancer patients were found to have:

• A higher rate of tumor necrosis. (What this means is unclear.)
• Fewer than expected ER-positive breast cancers, but most tumors in young women were ER-positive.
• A higher rate (25%) of HER2-positive breast cancers.
• More high grade tumors (two-thirds of young women).
• More triple-negative breast cancers (TNBC).
• Fewer ER-positive, HER2-negative breast cancers.
• More luminal B tumors (ER+, PR- and HER2+) than luminal A (ER+, PR+ and HER2-) breast cancers.

Why does this matter? Different types of tumors have different survival and treatment outcomes.

Age does not impact survival for women with HER2-positive tumors    

Age is NOT predictive of disease outcomes for women with HER2-positive tumors— young and old women with HER2-positive tumors had similar survival outcomes. Dr. Partridge asserted that: "Treatment principles should be similar regardless of age for women with HER2-positive tumors."

The most treatable tumor type has poorer outcomes among young women

ER-positive/HER2-negative tumors are the "most treatable" according to Dr. Partridge.  More treatment options are available for women with this type of breast cancer, and outcomes from those treatments can be robust. However, results of NCCN reviews highlight that outcomes are worse for young women with ER-positive, HER2-negative tumors versus older women and even more so for those with luminal A tumors. So why do young women with ER-positive/HER2-negative tumors have poorer outcomes?

Dr. Partridge proposed 3 broad hypotheses (which are not mutually exclusive) on why young women with ER-positive/HER2-negative breast cancer have poorer outcomes:

1.   Inherited mutations

24% of young women in the YWS (35 years or younger) had a germline (hereditary) mutation. This parallels The Cancer Genome Atlas (the National Cancer Institute’s study and categorization of tumor types and changes) where 26% of young women (34 years or younger) had a germline mutation versus 9% of older women (older than 35).

2.   Somatic gene changes

There were no differences in genetic changes within the tumors (somatic changes) of young women versus older women for those with Luminal B, HER2-positive or triple-negative tumors.

Younger women with luminal A tumors had fewer mutations in the tumor in the P1K3CA gene and more in the ARID1A gene. It remains to be determined how or if this correlated change impacts breast cancer outcomes.

3.   Proliferation gene signatures

Developmental changes in breast tissue after pregnancy may lead to differences in breast cancer outcomes. Research on mice suggests that mammary involution (shrinkage of breast tissue) that occur after pregnancy may affect cancer outcomes. It is unclear whether similar effects occur in humans.

Limitations:

The Young Women's Study is a prospective observational study of young women with breast cancer. It is an ongoing evaluation of prospective outcomes with an estimated completion data of 2025—current observations are limited to the study’s initial findings. Because it is an observational study, the correlations observed must be tested to determine whether or not they cause the findings.

The Young Women's Study did not enroll older women as a control group. For comparisons to older women, parallel studies were considered.  It is possible that there are some underlying differences between the populations of women in different studies. However, similar results were seen in the younger women of other studies.

Share your thoughts on this XRAYS article by taking our brief survey.

Posted 1/7/19