What You Need to Know About Estrogen and the KRAS-variant


Joanne Weidhaas is MiraKind’s founder and one of the scientists responsible for discovering the KRAS-variant, an inherited genetic mutation which predicts an increased risk of cancer. Following this breakthrough, Dr. Weidhaas and her team of researchers began exploring the connection between estrogen and breast cancer risk, particularly as it pertains to individuals who test positive for the KRAS-variant.estrogen and the KRAS-variant

Why the interest in estrogen?

The role of estrogen and hormone replacement therapy (HRT) has been a long and complicated tale. For decades, HRT was heralded as a wonderful solution for the woes of menopause for all women. However, in 2002, the Women’s Health Initiative (WHI) a long-term national health study, published a report claiming that HRT posed a significant risk of breast cancer and breast cancer death. Suddenly, HRT was abruptly stopped on millions of women and withheld from millions of others.

Follow-up studies contradicted the original findings from the WHI study, indicating that one size does not fit all, and in fact, estrogen appears to protect certain sub-groups of women from developing breast cancer, while also providing significant relief from menopause symptoms.

Unfortunately, much of this updated information has been lost in the muddle of confusion following the WHI study, and women are left struggling to define their own course for managing menopause and its many symptoms.

The following is some background about menopause, its symptoms, and the importance of being an advocate for your own health.

What is menopause and what are its symptoms?

Perimenopause marks the time in a woman’s life when the production of estrogen by the ovaries decreases significantly. A change in the frequency of one’s menstrual cycles and ultimately, a complete cessation of menstruation and fertility, follows shortly after this drop in hormones. Menopause officially begins when a woman has not had a period for 12 consecutive months, and usually occurs in a woman’s late 40s or early 50s, accompanied by a slew of symptoms, including fatigue, depression, weight gain, hot flashes and even changes in one’s cancer risk — the list goes on and on. These symptoms of menopause may leave menopausal women feeling frustrated by changes in their body and mood. Premenopausal women often dread such changes.

Menopause is natural.

It is important to remember that perimenopause (the period directly preceding menopause when hormone levels begin to shift) and menopause are natural and unavoidable aspects of any woman’s life. While every woman’s experience with menopause is different, acknowledging feelings of fear, confusion or anxiety about menopause and channeling them into action and education — especially when it comes to cancer risk is critical. Diet awareness, fruit and vegetable consumption, consistent exercise and adequate sleep are just a few of the lifestyle considerations we can make to best prepare for and manage menopause. Hormone replacement therapy is also a common option for women interested in relieving their menopausal symptoms. Dr. Weidhaas and her researchers further explore this topic below.

Menopause provides an opportunity.

Menopause provides a unique, empowering opportunity for women to take their health into their own hands. However, making decisions about hormone therapy and withdrawal can be confusing. Asking questions, talking to your doctor about your hormone-related options and being your own advocate will set you up for making crucial, informed decisions.

What is there to know about estrogen and the KRAS-variant?

Although high estrogen can increase primary breast cancer risk for some women, we have found that for women with the KRAS-variant, the opposite is true, i.e. estrogen may protect them from breast cancer! Could it be that KRAS-variant patients represent one of the sub-groups for whom estrogen actually helps protect against breast cancer in the WHI study? The MiraKind research team investigated this question, presented in a paper titled “Estrogen withdrawal, increased breast cancer risk and the KRAS-variant” in which they collected demographic and health data from approximately 2,000 breast cancer survivors. Read below for a summary of the main findings of this paper. The study was conducted by Dr. Weidhaas and MiraKind to investigate the impact of estrogen levels on breast cancer risk for KRAS-variant patients. Through a collaboration with the Army of Women, Dr. Weidhaas was able to collect data from 2000 breast cancer survivors, as well as include data from a group of KRAS-variant positive women without breast cancer.

Three Key Takeaways

1. Estrogen withdrawal and a low estrogen state appear to increase breast cancer risk for women with the KRAS-variant.

The research team found that when comparing women with the KRAS-variant with, versus without breast cancer, that KRAS-variant women with breast cancer were more likely to be thinner, and have fewer pregnancies than women with the KRAS-variant without cancer.

Furthermore, the team collected data on hormone replacement therapy (HRT) use, duration, and type among study participants. It was found that women who had tested positive for the KRAS-variant gene mutation who had stopped HRT were significantly more likely to be diagnosed with Triple Negative Breast Cancer (TNBC) than KRAS-variant positive women who were currently using HRT or had never used HRT. These findings were supported by further research in the lab, where normal breast cells that underwent estrogen withdrawal were transformed into breast cancer cells.

Overall, these findings suggest that aggressive breast cancer risk may be triggered in KRAS-variant women by lower baseline estrogen or estrogen withdrawal. Abrupt estrogen withdrawal, as found with oophorectomy, discontinuation of HRT or in cell experiments, may lead to the development of breast cancer cells and the development of aggressive breast tumors.

2. Women with the KRAS-variant are at a greater risk for Multiple Primary Breast Cancer, meaning they may have multiple separate breast cancers at the time of diagnosis, or, develop a second, independent breast cancer after their first breast cancer.

Overall, these findings suggest that there might be an event that triggers cancer in KRAS-variant women, or, that treatment for breast cancer, which consists of estrogen withdrawal for most, may, in fact, be a risk for a second independent breast cancer. Studies are continuing at MiraKind to better define the best approach to minimize second cancer risk for KRAS-variant women.

3. Because women with the KRAS-variant may be a sub-group where estrogen protects against breast cancer development, knowing a woman’s KRAS-variant status may provide additional useful information to help doctors and patients navigate the challenging decisions around estrogen management and HRT use at perimenopause and beyond

For all women, menopause presents an oftentimes daunting challenge. However, it has been shown that KRAS-variant individuals are unique in the way that their body uses hormones to protect against cancer. These findings including evidence that estrogen is protective for KRAS-variant women can help alleviate our concerns regarding hormone-related decisions, and spur a positive course of action. If you fit this profile as a KRAS-variant-positive woman, do not be afraid to take a step back and look at your hormone regimen, ask your doctor questions, explore our site, and be a fierce advocate for your health. If you are interested in determining your KRAS-variant status and assisting us in our research, we invite you to participate in one of our studies.

MiraKind is here for you, too.

We strive to be a resource aimed at providing KRAS-variant patients with information to demystify the complexities of genetics, cancer-risk and hormone management. In addition, we provide a monthly newsletter with news about our research and how it may impact you and your family members.

Read more about menopause and myths about hormone replacement therapy


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Any discussion of medical management options on this website is for general informational purposes only and does not constitute a medical recommendation. All medical management decisions should be made based on consultation between each patient and his or her healthcare professional.

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