Hormones and Breast Cancer Risk: What’s the Deal?
While most people diagnosed with breast cancer will be over the age of 50, we’re seeing more women (and those assigned female at birth) receiving a diagnosis of breast cancer in their 40s, 30s, and even 20s. This does not mean that you need to panic about breast cancer. What it means is that more than ever it’s important to be aware of your own breast health and your personal risk factors to be proactive in a way that makes sense for you. This is why starting the conversation now is so vital, because understanding what may or may not significantly impact your own personal risk is the first step in deciding what’s right for you.
So let’s talk about hormones because, for many, they will play a significant role in both risk of breast cancer and management after diagnosis.
Estrogen is the primary hormonal driver in many cases of breast cancer. While we’ve known for a long time that estrogen can fuel breast cancer by promoting proliferation (growth) of breast cancer cells, new research has shown that estrogen also directly alters how cells repair DNA (poor DNA repair can lead to abnormal cells that continue to grow and divide rapidly - ie. cancer cells). Increased exposure to higher estrogen levels has been a known risk factor for years (ex. onset of your period before age 11 and/or onset of menopause past the age of 55). Analysis of 7 studies found that women with higher levels of estrogen had a modestly increased risk of breast cancer before menopause.
Progesterone status (whether or not progesterone receptors are present on breast cancer cells) is always noted in a breast cancer diagnosis but unlike estrogen it’s not considered a key target or driver of breast cancer, the way estrogen is. However, linked within the increased risk of breast cancer when your period starts before age 11 and/or menopause happens after the age of 55 is the connection with a higher total number of ovulatory cycles, which is when progesterone is at its highest. Progesterone does help sensitize breast cancer cells to the actions of growth factors (ex. EGFR), meaning it doesn’t have the same direct impact on breast cancer cell proliferation as estrogen but it makes it a lot easier for that to keep happening. Additionally, when someone is diagnosed with breast cancer, if it’s progesterone positive they will likely respond better to endocrine therapies (ex. Tamoxifen or Letrozole) and have better long-term outcomes.
Hormone Replacement Therapy
There is still a lot of fear around the use of hormone replacement therapy (HRT or BHRT - Bioidentical Hormone Replacement Therapy), driven by the WHI (Women’s Health Initiative) study and the MWS (Million Women Study), which were published in the 1990s. These studies raised concerns around the safety of hormone replacement therapy (Estradiol + Progestin), especially as it pertained to breast cancer risk.
What continues to throw people off today is the reality that there is still a lot of widespread confusion and uncertainty among doctors and patients when it comes to the use and safety of HRT. Women can be on HRT for up to 5 years before they’ll have any increased risk of breast cancer. Overall the risk of breast cancer related to HRT is small and decreases progressively after treatment is stopped.
Research has shown the following, consistently:
1. Women who are on estrogen-only therapy (ie. women without a uterus who do not absolutely need progesterone when on estrogen therapy) can be on this for 7 years before their risk of breast cancer may start to increase.
2. Women who are on estrogen and progesterone therapy can be on this for up to 5 years before the risk of breast cancer will start to increase → this risk appears to be lower if they take oral micronized progesterone and not progestins (meaning they’re using bioidentical progesterone).
3. The increased risk of breast cancer with HRT has been primarily associated with the use of synthetic progestogen (or progestins) alongside estrogen therapy and that risk may be lower when estrogen is combined with oral micronized progesterone (ex. Prometrium).
4. Risk of breast cancer decreases after hormone therapy is stopped, no matter how long someone was on it for.
Overall, when it comes to breast cancer risk, HRT (combined estrogen and progesterone) will not increase a woman’s risk of breast cancer if she uses it for 5 years. After the 5 year mark, for every 1,000 women on HRT there will be 4 extra cases of breast cancer (for reference, for every 1000 women who consume 2+ alcoholic drinks per day there will be an extra 5 cases of breast cancer and for every 1000 women who are overweight there will be an extra 24 cases of breast cancer).
One important thing to be aware of is that because of the significantly increased risk of breast cancer in women who are overweight or obese, recent studies have shown that these women are at a significantly higher risk of developing breast cancer while on hormone therapy. For this reason it’s always important to consider your own health, wellness and risk factors when deciding whether HRT is right for you.
Hormonal Contraceptives (oral birth control and the IUD)
When it comes to breast cancer risk, there is a slight (around 7%) increased relative risk of breast cancer in women who use oral contraceptives for any length of time. Women who are on oral contraceptives have a 20-24% increased relative risk of breast cancer (which does not seem to increase with continued use) but the good news is that this risk declines after stopping and after 10 years off oral contraceptives there is no evidence of any increased risk of breast cancer. Another study found that the slight increase in risk of breast cancer was most pronounced in women who were on a triphasic oral contraceptive (where there are 3 doses of progestin and estrogen throughout the month). Additionally, the risk seems to be smaller for women who use oral contraceptives after their first full-term pregnancy.
Progestin-only oral contraceptives have also been shown in research to increase the risk of breast cancer more significantly than combined estrogen + progestin oral contraceptives. Research analyzing data from 9,498 women who developed invasive breast cancer between ages 20 to 49 found that use of progestogen-only hormonal contraceptives were associated with a 20-30% higher relative risk of breast cancer. As a note, progestin-only IUDs also showed an increased relative risk of breast cancer of around 30-32%.
Something really important to be aware of as you’re reading these numbers is that this is an increase in relative risk. For every 1000 women on combined oral contraceptives (estrogen + progestin) there will be an additional 4 cases of breast cancer. This means women who should be especially concerned about taking any type of hormonal contraceptive are those who are already at a higher risk of breast cancer, (ex. confirmed BRCA mutation). For the average woman the increased risk is similar to being on HRT and should always be considered against the benefits of this therapy.
Vaginal Estrogen
This is often used in women in perimenopause and menopause to help protect vaginal tissue and reduce discomfort, irritation, and lower the risk of recurrent UTIs that can occur when estrogen levels start to decline. When it comes to breast cancer risk this is absolutely the safest application of hormone therapy, as research has shown that it does not increase a woman’s risk of breast cancer. In fact, it’s even safe to use in someone who has a history of hormone-sensitive breast cancer (but the decision should always be made alongside your health care team in cases of a history of breast cancer to ensure this is the right choice).
Remember that estrogen and progesterone play such vital roles in your overall wellness. There’s no need to fear these hormones but sometimes we can lose sight of the risks when we’re focused solely on the benefits of hormonal treatment. For most women the benefits will outweigh the risks but I always want to ensure women are well-informed and able to fully consent to any treatment they move forward with.
A Final Word
If you have questions or concerns around your own breast health, hormone levels, or breast cancer risk, never hesitate to reach out. There are so many ways you can support your hormonal health and figuring out the best way forward, for you, is what good health care should always be focused on!
Ready to make a change?
If you're searching for more guidance and understanding of how you can support your breast health or address breast cancer concerns with naturopathic medicine, you can book a complimentary consult with me here.
Yours in health,
Dr. Hayhlee Clarence, ND
REFERENCES
1. https://www.nature.com/articles/s41586-023-06057-w
2. https://www.menopause.org/for-women/menopauseflashes/menopause-symptoms-and-t reatments/the-experts-do-agree-about-hormone-therapy
3. https://www.menopause.org/for-women/menopauseflashes/menopause-symptoms-and-t reatments/news-you-can-use-about-hormone-therapy
4. https://pubmed.ncbi.nlm.nih.gov/8656904/ 5. https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004188 6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862044/