By T. Salewa Oseni, MD, as told to Barbara Brody
For many years, anyone with breast cancer that had spread to the lymph nodes automatically got chemotherapy. This treatment stops or slows the growth of rapidly-dividing cancer cells, yet it’s not without downsides. In addition to well-known side effects like nausea and hair loss, it may also cause nerve damage, lead to cognitive issues, and raise the risk infections -- among other problems.
Yet chemo was our hammer, and when you have a hammer, everything is a nail. For a while it was the best -- and only -- means we had to fight against cancer that appeared to be spreading. But using it so often meant that many people were being overtreated and getting all of the downsides without many, if any, benefits. A landmark 2018 study revealed that up to 70% of women with breast cancer could safely forgo chemo.
Nowadays, when a woman is diagnosed with breast cancer, we discuss not only the size of the tumor and the stage of the cancer but also the tumor’s characteristics: What’s driving it, and how aggressive is it? That helps us figure out how aggressive to be when treating it. We also have to factor in a woman’s age and, perhaps more importantly, whether or not she has gone through menopause.
Why Menopause Matters
Menopausal status always plays some role with regard to breast cancer for a few reasons. For starters, breast cancer tends to be more aggressive when it’s diagnosed in younger, premenopausal women than when it’s found in older, postmenopausal women.
Menopause also matters in terms of the specific treatments that might work for a patient: If you have a hormonally-driven cancer (more on that below), your menopausal status will impact the type of anti-estrogen treatment you can use. Arimidex (anastrozole), for instance, is only used in post-menopausal women; it isn’t as effective in pre-menopausal breast cancer because the ovaries are still producing estrogen. If you haven’t yet gone through menopause and are a candidate for this type of therapy, your doctor would likely prescribe tamoxifen instead.
Hormone Receptors, HER2, and Tumor Biology
Whether or not you’re eligible for a hormonal treatment, you and your doctor still need to figure out if you ought to get chemotherapy. Generally speaking, women with very early-stage cancer (such as stage I) require the least aggressive treatment so they can often skip chemo. Those with more advanced cancer (stage II-III) require more aggressive therapy, so chemotherapy is usually warranted. However, even in this group some women may not require chemotherapy. Figuring out how to advise this group is more complicated.
This decision to give chemotherapy can be especially confusing for women whose cancer is hormone receptor-positive (HR-positive) but HER2-negative. (HER2 is a growth receptor protein found on the surface of some breast cancer cells. It‘s typically is associated with increased aggressiveness.)
If your cancer is HR-positive, it means that it has receptors for estrogen and/or progesterone. This kind of cancer usually responds well to hormonal therapies that block these receptors. If it’s HER2-positive, it will probably respond well to drugs designed to block this protein.
People with stage II or III cancer who are negative for estrogen and progesterone receptors as well as HER2 (aka “triple negative”) usually need chemotherapy, because they won’t benefit from estrogen-blocking therapies or HER2-blockers. Women who are HR-negative and HER2-positive will probably need it as well, since they can use targeted therapy but not hormonal therapy.
On the flip side, those who are HR-positive and HER2-positive can often skip the most aggressive types of chemotherapy (such as anthracyclines), because they do well on a combination of hormonal medication and drugs that target HER2 receptors.
What to do with those who are HR-positive but HER2 negative? Will hormonal medication be enough, or do these patients -- who aren’t candidates for drugs that target HER2 -- also need chemo? That’s where a genomic test comes in.
Oncotype Dx analyzes the expression of 21 genes in women with HR-positive, HER2-negative breast cancer and assigns them a score based on whether their risk of having a recurrence is low, intermediate, or high. If your score is low, you can likely bypass chemo. If your score is high, chemo is advisable.
If you end up in the intermediate group, you’re once again in unclear territory, yet this is where many breast cancer patients find themselves.
Weighing the Pros and Cons
If you’re a woman with stage II or III breast cancer, your cancer is HR-positive but HER2-negative, and your Oncotype Dx score comes back intermediate, deciding for or against chemo used to come down to personal risk tolerance. Now, thanks to a study called TAILORx, we know that menopause status should influence the decision. This study found that postmenopausal women with an intermediate Oncotype Dx score did not get any benefit from chemotherapy.
The TAILORx trial applied only to women whose cancer didn’t reach the lymph nodes, but another study called RxPONDER answered a similar question in women with lymph node involvement. As with TAILORx, the RxPONDER trial found that the majority of postmenopausal women did not receive benefit from chemotherapy. For premenopausal women under age 50, however, the addition of chemotherapy made a significant difference: Five years after treatment, 94% of the premenopausal women who opted for chemotherapy plus hormone therapy did not have invasive cancer (compared to 89% of those who only had hormone therapy).
You should also keep in mind that if you’re premenopausal and in your early- to mid-40s, chemotherapy might permanently push you into early menopause. For women who are younger, the chemo-induced absence of periods is more apt to be temporary, though it’s still wise to discuss fertility preservation if you hope to have children in the future.
Ultimately only you and your doctor can decide which treatments are right for you, but talking about whether or not you’ve gone through menopause should always be part of the discussion.