Studies Show the Breast Cancer Index Can Help Guide Treatment Strategy for Patients with Early-Stage Invasive Breast Cancer

The Breast Cancer Index (BCI) test is a quantitative assay based on the expression of 11 genes that may help patients with estrogen receptor–positive (ER+), early-stage breast cancers, in consultation with their oncologists, to decide whether they should extend endocrine therapy beyond 5 years.^1-3 Use of the BCI test is limited to ER+ early-stage breast cancer patients with lymph node–negative (LN–) or lymph node–positive (LN+; with 1-3 positive nodes) invasive disease without distant recurrence.⁴

The BCI combines 2 complementary gene expression signatures that assess proliferative and estrogen signaling pathways; it reports 2 distinct results: BCI Prognostic and BCI Predictive.^1,2,4,5

• BCI Prognostic: Reports a patient’s risk of late distant recurrence (from 5-10 years) as well as an overall risk of recurrence (years 0-10)^1,2
  • BCI Prognostic is reported as a percent risk of distant recurrence⁴
  • The patient’s risk of late distant recurrence (years 5-10) is also categorized as low or high based on prespecified cut points shown on a graph underneath the result⁴
• BCI Predictive: Reports a patient’s likelihood of benefit from extended endocrine therapy (years 5-10)³
  • The patient’s likelihood of benefiting from extended endocrine therapy is reported as either high or low⁴
• Given the composition of the test and the independent reporting of the Prognostic and Predictive components, 4 different test results are possible.

A low result for both the BCI Prognostic and the BCI Predictive components, when combined with a physician’s full medical assessment and other clinical findings, may support a decision to stop endocrine therapy after completing 5 years, whereas a high result for both may support a decision to extend endocrine therapy.⁴ As with all testing, BCI test results must be considered along with other clinical information.

Clinical Significance of the BCI Test

Whereas extending endocrine therapy beyond 5 years has been shown to benefit some women, only about 3% to 5% actually benefit from extending antiestrogen therapy beyond 5 years.^1-4 Extended endocrine therapy is also associated with side effects that can affect quality of life (eg, hot flashes), as well as potentially serious health risks (eg, endometrial cancer, bone fractures). BCI test results may help with the decision to extend endocrine therapy from 5 to 10 years.

Case Studies

Many women on endocrine treatment report struggling with troublesome side effects. Often this may lead to lack of adherence to or noncompliance with the treatment plan. Frequently, patients ask whether they should continue the endocrine treatment past year 5. They may inquire about clinical data or diagnostic tests that can help make this decision with their healthcare team. The BCI provides additional information about the individual’s risk of recurrence beyond year 5 and the likelihood of benefiting from extended therapy and may help encourage compliance in those who opt to continue.

Case 1. Low Risk of Late Recurrence, Low Likelihood of Benefit

A 65-year-old female breast radiologist with T2N0 intermediate, Ki-67 5%, Oncotype DX score 28 (intermediate risk) breast cancer received 5 years of tamoxifen following chemotherapy. Tamoxifen was chosen as her endocrine therapy because of her history of rheumatoid arthritis.

At the 5-year mark, this very risk-averse patient experienced cardiomyopathy. She had gained 20 lbs, and her physician reported that it was difficult to separate tamoxifen-related side effects from other medical issues. The tamoxifen was continued, however, because of the size of the tumor and the intermediate Oncotype DX score. A BCI test was performed to inform the decision of whether to continue endocrine therapy beyond year 5.

The BCI Prognostic result of 3.8%* indicated that there was a low risk of late distant recurrence, and the Predictive result indicated that there was a low likelihood the patient would benefit from extended endocrine therapy. After discussing the BCI results, the physician and patient decided to stop the tamoxifen therapy.

Case 2. High Risk of Late Recurrence, High Likelihood of Benefit

A 52-year-old woman presented with a 1.6-cm, grade 2, T1cN1 tumor with a 0.25-mm metastasis. Following wide local excision and radiation, she received adjuvant chemotherapy and began endocrine therapy with tamoxifen.

The patient remained on tamoxifen for 5 years and then switched to exemestane, an aromatase inhibitor. After 2.5 years on exemestane, patient complaints of decreased libido, achiness, and vaginal dryness prompted the ordering of the BCI test.

The BCI test revealed that the patient was at high risk of late breast cancer recurrence (Prognostic result of 7.8%*) and was highly likely to benefit from extended endocrine therapy. Given the higher risk of disease progression and the high likelihood of benefit from continuing endocrine therapy, the patient felt that she could tolerate the side effects. She decided to continue the exemestane therapy and possibly switch back to tamoxifen if the side effects became intolerable.

Case 3. Low Risk of Late Recurrence, Low Likelihood of Benefit

A 37-year-old woman presented with an 8-mm nodule. Core biopsy revealed a grade 2, ER+/progesterone receptor–positive (PR+), Oncotype DX score of 16 (low risk), stage T1bN0 tumor. Chemotherapy was ruled out, and endocrine therapy was initiated. The patient reported significant endocrine therapy–related side effects (ie, decreased libido, irregular menses, and pelvic pain). After 2 years 9 months of therapy, the patient wanted to know how much longer she needed to stay on therapy.

A BCI test was performed. The BCI Prognostic result was 2.6%, indicating that the risk of late breast cancer recurrence was low, while the BCI Predictive result indicated that the patient was unlikely to benefit from extended endocrine therapy. Because both her risk of late recurrence and benefit of extended therapy were low, the patient decided to stop therapy after 5 years, at which point she wanted to discuss considerations for getting pregnant.

Case 4. High Risk of Late Recurrence, Low Likelihood of Benefit

In 2008, a 46-year-old premenopausal woman was diagnosed with a stage IIA node-negative breast cancer. The 2.5-cm tumor in her right breast was ER+/PR+, HER2–, and had an Oncotype DX score of 10 (low risk). Treatment with adjuvant endocrine therapy with tamoxifen was initiated.

The patient remained on tamoxifen for 6 years, during which time she gained weight and reported fatigue and hot flashes. In 2014 (the 6-year point), a BCI test was performed to help inform the decision of whether to continue on tamoxifen.

The BCI report indicated that the patient’s risk of late recurrence was high (Prognostic result of 6.5%*), but the likelihood that she would benefit from extended endocrine therapy was low. Concerned about the high risk of late recurrence, the patient decided to continue tamoxifen therapy.

*Between years 5-10.

References

1. Zhang Y, Schnabel CA, Schroeder BE, et al. Breast Cancer Index identifies early-stage estrogen receptor–positive breast cancer patients at risk for early- and late-distant recurrence. Clin Cancer Res. 2013;19:4196-4205.
2. Sgroi DC, Sestak I, Cuzick J, et al. Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population. Lancet Oncol. 2013;14:1067-1076.
3. Sgroi DC, Carney E, Zarrella E, et al. Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker. J Natl Cancer Inst. 2013;105:1036-1042.
4. Breast Cancer Index website. www.breastcancerindex.com. Accessed August 25, 2016.
5. Ma XJ, Salunga R, Dahiya S, et al. A five-gene molecular grade index and HOXB13:IL17BR are complementary prognostic factors in early stage breast cancer. Clin Cancer Res. 2008;14:2601-2608.