Breast Cancer Basics: Hormonal Therapy (How To Decide If You Should You Take It For 5 Or 10 Years)

This is a big question asked by most hormone receptor positive breast cancer survivors. The data clearly shows an improvement in outcomes when taking 5 years of endocrine therapy, and recent studies report additional benefits when continuing to take these drugs for an even longer duration. Studies clearly show that recurrences continue to occur amongst survivors who complete 5 years of endocrine therapy.
Association between Pathological Nodal Status and the Risk of Distant Recurrence or Death from Breast Cancer during the 20-Year Study Period. Shown are data regarding the risk of distant recurrence (Panel A) and death from breast cancer (Panel B) among 74,194 women with ER-positive T1 or T2 disease who were enrolled in 78 trials at year 0 and were scheduled to receive 5 years of endocrine therapy. (Data for an- other 10,200 women who enrolled in 10 trials after year 0 are not shown here.) The risk was calculated according to the patients’ pathological nodal status at the time of diagnosis: N0, N1–3, or N4–9. The number of events and annual rate are shown for the preceding period (e.g., data for years 0 to 4 are shown at 5 years). The I bars indicate 95% confidence intervals. The dashed lines indicate that the event rate is for the whole 5-year period, rather than for individual years, as is otherwise shown. The annual rate of death from breast cancer was estimated by subtracting the death rate in women without recurrence from the rate in all women.

What’s the absolute benefit of extending endocrine therapy beyond 5 years?

According to clinical trials, most patients on extended endocrine therapy are not likely to benefit. Across 4 major trials, only about 3-5% of patients benefited from extended endocrine therapy. This is why it is important to understand whether you personally are among the group of women who are likely to benefit from extended treatment.

ASCO Guidelines Updated in 2018
The updated guidelines are based on the results of six large trials looking at whether taking an aromatase inhibitor for more than 5 years offered additional benefits. The studies found that extended aromatase inhibitor treatment didn’t seem to improve overall survival, but it did significantly reduce the risk of breast cancer recurrence and the risk of breast cancer developing in the opposite breast. Based on data from prospective randomized clinical trials, the ASCO adjuvant endocrine therapy Expert Panel recommends extended duration with any one of the following strategies:
  • AI for up to a total of 10 years; or
  • tamoxifen for 2 to 3 years followed by AI for 7 to 8 years; or
  • tamoxifen for 5 years followed by AI for 5 years; or
  • tamoxifen for 10 years.
For postmenopausal women diagnosed with early-stage, hormone-receptor-positive breast cancer, the updated guidelines say:
  • Many women diagnosed with node-negative disease may be good candidates for 10 years of treatment with an aromatase inhibitor after breast cancer surgery. Still, since the recurrence risk for node-negative disease is generally lower than the recurrence risk for node-positive disease, the benefits will likely be smaller for this group of women. Women with node-negative disease with a low risk of recurrence should not routinely be offered extended hormonal therapy.
  • Women diagnosed with node-positive disease should be offered extended aromatase inhibitor treatment after breast cancer surgery, for up to a total of 10 years of aromatase inhibitor treatment.
  • Women who receive extended hormonal therapy treatment after surgery should received no more than 10 years of hormonal therapy treatment.
  • A woman’s risk of a new, second breast cancer and her risk of breast cancer in the opposite breast should be factors in deciding whether a woman receives extended hormonal therapy treatment.
  • Ten years of hormonal therapy comes with risks and side effects, as well as benefits. Women and their doctors should weigh these risks against the benefits when making decisions about extended hormonal therapy treatment.

Online Calculator Can Determine Your Risk of Recurrence (CTS5 Calculator)

The CTS5 calculator is proven to be effective at predicting relapse of breast cancer after 5 years of hormone therapy treatment. It categorizes female breast cancer patients (pre- or postmenopausal) into three risk groups: high, medium and low. Low risk group: these breast cancer survivors are at a significantly low risk of their breast cancer returning five to 10 years after their initial five year endocrine therapy treatment. This risk is so low, it would not warrant extending endocrine therapy to ten years.

Genomic Test (Breast Cancer Index “BCI”) Predicts Risk of Recurrence After 5 Years and the Potential Benefit of Continuing Hormone Therapy

The Breast Cancer Index (BCI) Test is a genomic test that is done on a sample of your breast cancer tumor that is in the pathology department (most pathology departments keep your tumor tissue for 10 years). This test examines the DNA of your cancer to assess genes associated with recurrence and probability of benefit of longterm endocrine therapy. The BCI intended for use in patients diagnosed with estrogen receptor-positive (ER+), lymph node-negative (LN-) or lymph node positive (LN+; with 1-3 positive nodes) early-stage, invasive breast cancer, who are recurrence-free. BCI provides:
  • Your risk of recurrence after 5-years of endocrine therapy
  • Your overall risk of distant recurrence (0-10 years) following an initial 5 years of endocrine therapy (LN- patients) or 5 years of endocrine therapy plus adjuvant chemotherapy (LN+ patients)
  • Your likelihood of benefit from extended (>5 year) endocrine therapy

Liquid Biopsies Are Not Standard, Yet, But They May Help You Anyway

As healthy and diseased tissue interact with the bloodstream, they release both cellular and genetic material into the circulation. These materials are referred to as circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs).
  • Circulating tumor cells (CTCs) are cells that have detached from a primary tumor and circulate in the bloodstream. CTCs may travel to other areas and create new tumors in different tissues or organs (metastases). Elevated CTCs at any time in the course of clinical treatment of metastic breast cancer are indicators of progression.
  • ctDNA stands for circulating tumor DNA. These fragments of non-cellular mutated DNA can find their way into blood through either apoptosis or necrosis of the solid tumor tissue. ctDNA can also be generated from circulating tumor cells (CTCs) that are released by a tumor into the blood stream, followed by degradation within the blood stream and a release of DNA contents.
Liquid biopsies are typically conducted with blood as the sample type, and are used to identify ctDNA or CTCs which are the most commonly evaluated indicators or drivers of cancer development. Although not yet standardly recommended in the conventional oncology guidelines (i.e. NCCN), oncologist may use liquid biopsies to determine if a prior cancer condition has recurred. The presence of tumor cells circulating in the blood has been associated with shortened survival from various solid tumor cancers. I use the Biocept Assay. Tracking the numerical trend of ctDNA or CTCs in the blood may give an indication of subclinical cancer. An increasing number would obviously be concerning, and a stable or declining number would be more reassuring. If you ask any academic breast cancer oncologist, they will tell you that these assays must be validated in large randomized controlled studies before they will be adopted by the national oncology guidelines. Nevertheless, many smaller clinical studies currently suggest that these assays are prognostic. If a patient wants to order this and knows that caveats, to me that is certainly reasonable.

Taking 5-additional years of endocrine therapy only makes sense if the benefits outweigh the risks

The decision to take an additional 5-years of endocrine therapy is often not a simple one. Weigh the potential benefits/risks and discuss this with your oncologist.