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

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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 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 tumors.
  • Young women under age 40 with ER-positive, 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 and endocrine therapy. However, compared to older women, young women on 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 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 endocrine therapy after their breast cancer diagnosis and want to become pregnant. Women with and mutations are eligible. Enrollment is estimated to be completed by June 2020.

During the POSITIVE trial, participants will:

  • interrupt 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, breast cancer, your chance of recurrence may differ from women diagnosed at older ages.
  • If you are a woman with a 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 in a gene that affects cancer predisposition.

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

Posted 1/7/19

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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


FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

This article is relevant for:

Women diagnosed with breast cancer at a young age

This article is also relevant for:

people with triple negative breast cancer

people with ER/PR + cancer

people with Her2-positive cancer

people with breast cancer

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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 ( 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 breast cancers.
  • More high grade tumors (two-thirds of young women).
  • More triple-negative breast cancers ().
  • Fewer ER-positive, 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 tumors    

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


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.


The Young Women's Study is a observational study of young women with breast cancer. It is an ongoing evaluation of 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

Expert Guidelines
Expert Guidelines

The National Comprehensive Cancer Network (NCCN) provides guidelines for fertility in people diagnosed with cancer. 

The NCCN recommends doctors discuss the following with adolescents and adults with cancer before treatment begins:

  • fertility plans and preferences
  • fertility preservation options, including:
    • whether therapy can be delayed long enough for a cycle of egg stimulation
    • cryopreservation
    • medications like GnRH agonist therapy during to preserve ovarian function in premenopausal women with breast cancer
  • the importance of follow-up with a gynecologist or fertility specialist to monitor ovarian function over time
  • the risks of infertility due to cancer and related treatment
  • the effects of treatment on breastfeeding
  • the importance of avoiding pregnancy and options for safe and effective birth control while in treatment
  • safe timing for considering pregnancy after treatment 
  • the emotional impact of discussions about fertility preservation
  • financial resources for fertility preservation
  • the effects of treatment on sexual function during and after treatment

Doctors should refer patients as indicated for the following services:

  • All patients who are interested in preserving their fertility should be referred to a fertility preservation clinic before starting treatment.
  • Patients who need assistance with complex medical decision-making should be referred to a mental health professional.
  • Patients who are experiencing sexual dysfunction should be referred to a sexual health specialist. 

Updated: 02/06/2022

Expert Guidelines
Expert Guidelines

The National Comprehensive Cancer Network (NCCN) recommends screening and treatment of distress as part of the recommended standard of care. 

These recommendations include:

  • Healthcare providers should inform patients, families and treatment teams that distress management is a key part of their medical care, and they should provide information about psychosocial services.
  • Ideally, healthcare providers should screen patients for distress at every medical visit— minimally at a patient’s initial visit and then as clinically indicated, especially with changes in disease status (i.e., remission, recurrence, progression or treatment-related complications).
  • Healthcare providers should assess and manage distress according to clinical practice guidelines.
  • Experts in psychosocial aspects of cancer should be readily available, either as staff members or by referral.
  • Assessments should include psychosocial issues (e.g., quality of life and patient and family satisfaction).

Patients should expect to receive distress screening and help at your doctor visits. If your distress isn’t addressed, ask for help. NCCN provides a "Distress During Cancer Care" pamphlet that provides more information.

The American Society for Clinical Oncology (ASCO) points out several therapies for anxiety and stress for patients to consider during or after cancer treatment:

  • acupuncture
  • massage
  • meditation, particularly mindfulness stress-reduction programs
  • music therapy
  • stress management therapy.
  • yoga 

Updated: 02/06/2022

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • Is it safe for me to become pregnant after treatment for breast cancer?
  • I have had breast cancer and I am interested in having children. What factors should I consider?
  • How might my cancer treatment affect my future ability to have children?
  • Are there ways to preserve my fertility? How might they impact my risk of cancer recurrence?
  • Before I start treatment, is there anything that I should know about preserving my fertility?
  • I am experiencing anxiety or distress, can you refer me to a mental health expert? 

Open Clinical Trials
Open Clinical Trials

The following research studies related to fertility preservation are enrolling patients.

Fertility preservation studies for women

Fertility preservation for men

  • NCT02972801: Testicular Tissue Cryopreservation for Fertility Preservation. Testicular tissue cryopreservation is an experimental procedure involving testicular tissue that is retrieved and frozen. This technique is reserved for young male patients, with the ultimate goal that their tissue may be used in the future to restore fertility when experimental techniques emerge from the research pipeline.

Updated: 09/29/2023

Peer Support
Peer Support

The following organizations offer peer support services for people with, or at high risk for breast cancer:

Updated: 05/07/2024

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