After 5 Years

Now What?

You were successfully treated for your estrogen-receptor positive (ER+) breast cancer and your doctor put you on anti-estrogen treatment. It’s been a few years and you want to know what’s next. You want to do what your healthcare team advises to prevent the cancer from coming back – but you also want to improve your quality of life. Perhaps no one told you about the potential side effects that go along with being on anti-estrogen therapy. Or maybe they did, but you didn’t anticipate that those side effects would have such a big impact on your daily life.

The decision making process for treatment planning beyond five years for the ER+ breast cancer survivor is complex. 

Here is what we already know: Anti-estrogen therapy is the standard of care to treat ER+ breast cancer.  So, for many patients, adjuvant treatment – treatment that is used after initial treatment — with typically tamoxifen (pre-menopausal) or an aromatase inhibitor (post-menopausal) for five years is used to prevent relapse or recurrence of that same breast cancer.

But what you may not know is that recent studies have shown a benefit in extending treatment beyond five years for some women and, without tools to help identify which women may benefit, the recommendation for many women has been to extend therapy for another five years.

However, in studies of ~20,000 women, benefit from an additional five years of anti-estrogen therapy was limited to ~3-5% of patients.  That means that the overwhelming majority of patients who extended anti-estrogen therapy beyond five years had no significant benefit.

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ER+ Breast Cancer: Not Just a Five-Year Disease

Estrogen receptor-positive (ER+) breast cancer – cancer where the body’s own estrogen may contribute to its growth1 is the most common type of breast cancer and accounts for 80% of breast cancer cases.2 The overall prognosis for women with early stage (stage I & II) ER+ breast cancer is generally favorable.  However, while survival rates for many cancers are measured with a five-year benchmark, ER+ breast cancer is not just a five-year disease.3-5 In fact, because each woman’s tumor differs biologically, some women may have a disease recurrence before year five, while others may have a recurrence beyond year five.3-4 Studies have shown that for some early stage ER+ breast cancer patients taking anti-estrogen therapy, there is a benefit to extending therapy for an additional five years.6-10 However, in clinical trials, that benefit was limited to only 3%–5% of the patients who were recurrence-free at the five-year mark. 6-10

Research is ongoing to determine the best course of treatment for women with estrogen-receptor positive breast cancer. This includes decisions about chemotherapy and duration of anti-estrogen therapy.

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About Anti-Estrogen Therapy

Anti-estrogen therapy, sometimes called hormone or endocrine therapy, is a type of treatment or drug that is specifically used to either deprive the body of estrogen or block the action of estrogen on breast cancer cells.2 It is prescribed to ER+ patients to reduce the risk of recurrence of the disease.2 The three main types of anti-estrogen therapy that are typically used to treat estrogen-receptor positive breast cancer are:

Selective estrogen-receptor response modulators (SERMs). SERMs block the effects of estrogen in the breast tissue by attaching to the estrogen receptors in breast cancer cells. Tamoxifen is the SERM most commonly used to treat breast cancer.11 The most common side effects of these drugs include hot flashes, vaginal dryness or discharge, fatigue, mood swings, and low libido.  Less frequent but serious safety issues include uterine cancers, blood clots, and stroke.12

Aromatase inhibitors. Aromatase inhibitors work by stopping the production of estrogen in postmenopausal women. Aromatase inhibitors block the enzyme aromatase, which turns the hormone androgen into small amounts of estrogen in the body. As a result, less estrogen is available to stimulate the growth of hormone-receptor-positive breast cancer cells. Because aromatase inhibitors can’t stop the ovaries from making estrogen these medications only work in postmenopausal women. The main sources of the hormone for those women are the adrenal glands and fat tissue, not the ovaries. Aromatase inhibitors include Arimidex (chemical name: anastrozole), Aromasin (chemical name: exemestane), and Femara (chemical name: letrozole).11

Common side effects of these drugs include joint stiffness, joint and muscle pain, hot flashes and night sweats, and vaginal dryness.12 Less frequent but serious safety issues such as osteoporosis, bone fractures, and heart disease have also been reported.12

Ovarian suppression. Ovarian suppression refers to any treatment that causes the ovaries to stop making estrogen. The ovaries can be suppressed in a few different ways including surgical removal of the ovaries (called oophorectomy) or radiation treatment of the ovaries, both of which permanently stop the ovaries from making hormones, and medical shutdown of the ovaries which temporarily stop the ovaries from making estrogen. Two of the most common ovarian shutdown medicines are Zoladex (chemical name: goserelin) and Lupron (chemical name: leuprolide).13

Zoladex and Lupron are both luteinizing hormone-releasing hormone (LHRH) agonists. These medicines work by telling the brain to stop the ovaries from making estrogen. The medicines are given as injections once a month for several months or every few months. Once you stop taking the medicine, the ovaries begin functioning again. The time it takes for the ovaries to recover can vary from woman to woman.13

For some patients with a breast cancer that may place them at a higher than average risk of recurrence (including those who are 35 years or younger or who underwent chemotherapy), ovarian suppression plus an aromatase inhibitor may be recommended by your doctor. Of note, all forms of ovarian suppression cause a rapid onset of menopause symptoms (hot flashes, night sweats, mood swings, vaginal dryness), which can be severe.13

Duration of Anti-Estrogen Therapy. Women with ER+ breast cancer are often prescribed anti-estrogen treatments for at least five years, and up to 10 years, to prevent recurrence of the disease.  But because these treatments are specifically designed to inhibit the role of naturally-occurring estrogen in the body, they are often associated with issues that range from day-to-day challenges such as muscle pain, hot flashes and sexual dysfunction which can significantly impact the patient’s quality of life, to less frequent but serious health issues such as osteoporosis, bone fractures, endometrial cancer and heart disease, depending on the type of anti-estrogen treatment.2

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Personalized Treatment

Breast cancer treatment plans no longer have to be “one-size fits all.” New information and tests are now available to help women better understand their risk of cancer recurrence, and what therapeutic approaches (both the type of therapies and duration of the therapy) are likely to be beneficial for their individual breast cancer. This knowledge can help women, together with their doctor, to make more confident and informed treatment decisions, and decrease anxiety.

At diagnosis, a tumor is assessed in multiple ways including size and tumor grade (the appearance of the cell growth), the rate of cell growth, and whether the cancer has spread to the lymph nodes. These features provide important information about your cancer and the extent of the disease, and how this affects your risk of cancer returning. Tumors are also assessed for hormone receptor and HER2 status. All of these features help your physician understand what treatments to recommend for you specifically.

Tests that evaluate risk of recurrence and likelihood of benefit from therapy

Researchers have found that gene expression profiling tests can help predict whether or not an early-stage breast cancer is likely to come back after initial treatment and if particular therapies are likely to be beneficial in the treatment of an individual patient.

Oncotype DX® helps doctors figure out a woman’s risk of early-stage, estrogen-receptor-positive breast cancer coming back (recurrence), as well as whether she is likely to benefit from chemotherapy in addition to anti-estrogen therapy after breast cancer surgery.

For example, recently, the Trial Assigning Individualized Options for Treatment (or TAILORx) trial showed that for women with early-stage hormone receptor-positive breast cancer who have a very low risk of recurrence based on Oncotype DX®, five-year recurrence rates are very low when postoperative treatment consists of hormone therapy alone.14

Breast Cancer IndexSM (BCI) is a non-invasive test that helps physicians and patients determine whether to extend anti-estrogen therapy from five to 10 years by assessing both the risk of breast cancer recurrence after year five and the likelihood of benefit from anti-estrogen therapy beyond five-years.

This test was validated in the well-known MA.17 clinical trial, where the group of patients with a low BCI Predictive index did not derive significant benefit from extended endocrine therapy, while the group of patients with a high BCI Predictive index derived substantial benefit.

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