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


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Fertility issues and family planning decisions are prominent concerns for young women with breast cancer. This XRAYS looks at Dr. Ann Partridge’s presentation at the 2018 San Antonio Breast Cancer symposium. Her talk, “Breast cancer in young women: Understanding differences to improve outcomes," focused on initial findings from the Young Women's Breast Cancer Study. Dr. Partridge’s research continues in the currently enrolling POSITIVE trial which tests whether women can safely interrupt adjuvant endocrine therapy in order to get pregnant. (1/7/19)

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STUDY AT A GLANCE

Dr. Ann Partridge of the Dana-Farber Cancer Institute was awarded the American Association of Cancer Research's 2018 award for Outstanding Investigator in Breast Cancer Research. Her talk—"Breast cancer in young women: Understanding differences to improve outcomes”—at the 2018 San Antonio Breast Cancer Symposium (SABCS) described her work on the Young Women's Breast Cancer Study to understand the needs of young women diagnosed with breast cancer. She also highlighted the POSITIVE trial, which was designed to determine whether it's safe for women to interrupt endocrine therapy in order to get pregnant.

This study is about:

The Young Women's Breast Cancer Study (YWS) is a multi-institution prospective clinical trial that is focused on understanding the biological, medical and psychosocial outcomes for young women diagnosed with breast cancer.

Why is this study important?

This study is designed to understand how young women differ from older women with breast cancer, examine the underlying reasons for those differences, and establish how to obtain the best outcomes for young women.

Study findings: 

Dr. Partridge and colleagues prospectively surveyed 1,302 women age 40 or younger at the time of their diagnosis about their breast cancer and their biological, medical and psychosocial outcomes.

The researchers found that:

  • The tumor types of participating young women with diagnosed breast cancer were more diverse and occurred in a different proportion than in the general population of women with breast cancer.
  • Age did not impact outcomes for women with HER2-positive tumors.
  • Young women under age 40 with ER-positive, HER2-negative breast cancer had the worst outcomes relative to the general population. In contrast, this tumor type in post-menopausal women responds well to treatment.

Among participants in the study:

  • 38% were somewhat or very concerned about fertility.
  • 68% discussed fertility issues with their healthcare providers.
  • 10% took steps to preserve fertility (e.g., cryopreservation).

The next step: Does temporary interruption of endocrine therapy alter outcomes?

Treatment for invasive breast cancer commonly includes surgical removal of the tumor followed by adjuvant chemotherapy and endocrine therapy. However, compared to older women, young women on adjuvant hormonal therapy are less likely to adhere to and more likely to discontinue treatment. This may reflect many factors, including fertility concerns and subsequent conception attempts, pregnancy and breastfeeding.

Dr. Partridge and colleagues launched the POSITIVE trial (Pregnancy Outcome and Safety of Interrupting Therapy in Endocrine Responsive Breast Cancer) in 2014 to address fertility concerns among young breast cancer patients. This trial prospectively evaluates the safety of interrupting endocrine therapy for childbearing attempt(s). (Endocrine therapy involves the use of drugs that block estrogen or progesterone from cancer cells or that stop production of one or both hormones.)

Currently, 330 of 500 participants are enrolled. This trial is still recruiting young women who are 18-42 years old, have completed 18-30 months of adjuvant endocrine therapy after their breast cancer diagnosis and want to become pregnant. Women with BRCA1 and BRCA2 mutations are eligible. Enrollment is estimated to be completed by June 2020.

During the POSITIVE trial, participants will:

  • interrupt adjuvant endocrine therapy for up to 2 years to allow conception and potential pregnancy and breastfeeding.
  • resume their endocrine therapy for a full course.
  • be followed to determine incidence of breast cancer recurrence, fertility and pregnancy, cancer outcomes and other psychosocial factors.

What does this mean for me?

  • If you are a young woman diagnosed with an ER-positive, HER2-negative breast cancer, your chance of recurrence may differ from women diagnosed at older ages.
  • If you are a woman with a HER2-positive tumor, current data suggest that risks and outcomes are similar among women of different ages; that is, treatments need not differ by age.
  • Note: Women diagnosed with breast cancer at a young age are more likely to have an inherited mutation in a gene that affects cancer predisposition.

If you are taking adjuvant endocrine therapy after a breast cancer diagnosis and are interested in becoming pregnant, you may be eligible for the POSITIVE study.

Questions to ask your health care provider

  • I have had breast cancer and I am interested in having children. What factors should I consider?
  • How might my cancer therapy affect my future ability to have children?
  • Are there ways to preserve my fertility? How might they impact my risk of cancer recurrence?

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

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 outcomes 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 the worst 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

References

Ann Partridge. "Breast Cancer in Young Women: Understanding Differences to Improve Outcomes." San Antonio Breast Cancer Symposium, AACR Outstanding Investigator Award in Breast Cancer Research lecture. Dec 7 2018.

POSITIVE trial: Pregnancy Outcome and Safety of Interrupting Therapy in Endocrine Responsive Breast Cancer

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FORCE XRAYS category: Breast cancer risk

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FORCE XRAYS category: Pregnancy and Fertility

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