Chemotherapy in premenopausal patients with breast cancer

EndoPredict® Breast Cancer Prognostic Test is the only second generation breast cancer recurrence gene expression test validated for premenopausal AND postmenopausal women with early-stage ER positive/HER2 negative breast cancer.

Information for clinicians

What's the chemotherapy effectiveness in premenopausal women?

Premenopausal women with early-stage ER positive/HER2 negative breast cancer can sometimes be overtreated with chemotherapy.1,2 At what point do the risks of chemotherapy and its side-effects outweigh the benefits for young women?

EndoPredict can answer this with its prediction of individual chemotherapy benefit, allowing you to determine at 10 years if the risk of chemotherapy is greater than the chemotherapy benefit for your individual patient. Premenopausal EPclin low-risk patients have on average a 3% risk of distant recurrence and an expected chemotherapy benefit of below 3%. Therefore, the 2-3% risk of more serious side-effects by chemotherapy outweighs the expected benefit from chemotherapy.

Every woman, regardless of her age or menopausal status, can know if she would benefit from chemotherapy or not.

 

Watch Myriad Genetics' ESMO 2022 Industry Satellite Symposium

Should we use genetic signatures for chemotherapy decisions in ER+/HER2- premenopausal patients? Dr. Anastasia Constantinidou shares key new data from ESMO Congress 2022 demonstrating how EndoPredict can help guide treatment decisions and avoid overtreatment for premenopausal women with ER+, HER2- early breast cancer.

Watch video

EndoPredict guides confident breast cancer treatment decisions with the future in mind

EndoPredict is the only second generation breast cancer recurrence test validated for premenopausal and postmenopausal women with early-stage breast cancer that is ER positive, HER2 negative, node negative or positive3-9 – and the only second generation test with level of evidence 1A data.10,11

New data provide EndoPredict with prospective proof of previous published validation studies to make a confident breast cancer prognosis and treatment decision for premenopausal women. This study shows that EndoPredict clearly identifies young women who might forego chemotherapy.12

EndoPredict is also the only test providing a 15-year recurrence risk for long-term breast cancer prognosis3 – learn more about EndoPredict and long-term recurrence risk.

How does EndoPredict perform compared to Oncotype DX® in premenopausal patients with node positive and node negative disease?

For the first generation Oncotype DX® test, two prospective randomized controlled trials are unclear about predicting chemotherapy benefit for node negative and node positive patients in a premenopausal setting, potentially leading to overtreatment in younger women.13,14

EndoPredict is the only second generation gene expression test validated in premenopausal women

EndoPredict clearly identifies a large group of low-risk women who would not benefit from adjuvant chemotherapy due to a very low recurrence risk.9

The association between EPclin Risk Score and 10‑year distant recurrence was evaluated in women with ER positive, HER2 negative primary breast cancer who were premenopausal at the time of diagnosis and received endocrine therapy only:

  • With EndoPredict 64.7% of all premenopausal patients were identified as EPclin low-risk
  • The EPclin high-risk group had a significantly increased risk of distant recurrence compared with low-risk (24% vs 3%)
  • Risk in the EPclin low-risk group remains below 10% regardless of nodal status

EndoPredict identifies low-risk premenopausal patients, regardless of nodal status

Not all premenopausal women with node positive ER+, HER2- breast cancer need to be overtreated. In the same premenopausal validation study:

  • 73% of node negative and 19% of node positive patients were identified as low-risk
  • With 10-year distant recurrence rates of 3% or less, these patients may avoid chemotherapy

Similar 10-year DRFS with or without ovarian function suppression

EPclin low-risk premenopausal women can be treated with endocrine therapy alone

Trials like RxPonder and TAILORx suggest the outcome of a multigene assay differs with menopausal status, with premenopausal women supposedly receiving a greater benefit from chemotherapy. However, it remains unclear whether the observed benefit seen in these Oncotype DX® trials is a direct chemotherapy effect or due to chemotherapy-induced ovarian function suppression (OFS).

The Constantinidou et al. 2022 study conducted an exploratory subgroup analysis comparing EPclin low-risk patients who did not (N=171) and did (N=214) receive OFS. Results showed similar 10-years DRFS in patients with and without OFS, with less than 5% distant recurrence after 10 years in both groups – EndoPredict identifies low-risk women that can be treated with endocrine therapy only, regardless of menopausal status.

Four year prospective outcome data of premenopausal women12

EndoPredict is the only second generation test which has prospective outcome data specifically in premenopausal patients with breast cancer.

Study details:

  • Prospective decision impact study on 99 premenopausal patients with 0-3 positive lymph nodes.12
  • No events in EPclin low-risk group (4 years DDFS: 100% compared to 94% in high-risk group, p=0.094)

Level of evidence 1A data confirm EndoPredict identifies low-risk patients with node positive disease10

Study details:

  • Prospective, randomized controlled, double-blind phase III study (UNIRAD) on 767 pre- or postmenopausal, clinically high-risk, chemotherapy-treated, node positive patients – 1 in 3 of patients were premenopausal.
  • Significant dichotomization between high- and low-risk patients
  • No events in the low-risk group with a median follow up of 55 months, despite the population being clinically high-risk
  • EndoPredict was the only significant independent prognostic factor in the multivariate analysis (including nodal status, grading and tumor size)

This is the first prospective validation data in a randomized controlled trial of a second generation test, and confirms previous prospective-retrospective validation data

EndoPredict identifies low-risk premenopausal women with node positive disease7

Despite all patients having node positive disease, in both pre- and postmenopausal women, those identified as low-risk by EndoPredict (12% and 15% respectively) had zero relapse at 10 years.

Study details:

  • The GEICAM/9906 study was the prospective-retrospective clinical validation of EndoPredict in 555 node positive, chemotherapy-treated, ER positive/HER2 negative breast cancer patients.
  • Patients were treated with endocrine therapy plus either six cycles of FEC or with four cycles of FEC followed by eight weekly courses of paclitaxel (FEC-P).

EndoPredict second generation test can be performed locally within a few days

EndoPredict Breast Cancer Prognostic Test is available to order by clinicians via numerous local labs in your country or outside of the EU also via Myriad Genetics’ central laboratory in Salt Lake City, USA.

References

  1. Cancello, Giuseppe, and Montagna, Emilia. “Treatment of breast cancer in young women: do we need more aggressive therapies?”. Journal of Thoracic Disease, vol. 5, Suppl 1, 2013, pp. S47-54
  2. Subhedar, Preeti D, and Sarah A McLaughlin. “Breast Cancer In The Young Patient: Review Of Therapy And Treatment Considerations“. Breast Cancer Management, vol 9, no. 2, Reviews 2020
  3. Filipits, Martin et al. “A New Molecular Predictor Of Distant Recurrence In ER-Positive, HER2-Negative Breast Cancer Adds Independent Information To Conventional Clinical Risk Factors“. Clinical Cancer Research, vol 17, no. 18, 2011, pp. 6012-6020
  4. Filipits, Martin et al. “Prediction Of Distant Recurrence Using Endopredict Among Women With ER+, HER2− Node-Positive And Node-Negative Breast Cancer Treated With Endocrine Therapy Only“. Clinical Cancer Research, vol 25, no. 13, 2019, pp. 3865-3872
  5. Buus, Richard et al. “Comparison Of Endopredict And Epclin With Oncotype DX Recurrence Score For Prediction Of Risk Of Distant Recurrence After Endocrine Therapy“. Journal Of The National Cancer Institute, vol 108, no. 11, 2016, p. djw149
  6. Sestak, Ivana et al. “Prediction Of Chemotherapy Benefit By Endopredict In Patients With Breast Cancer Who Received Adjuvant Endocrine Therapy Plus Chemotherapy Or Endocrine Therapy Alone“. Breast Cancer Research And Treatment, vol 176, no. 2, 2019, pp. 377-386
  7. Martin, Miguel et al. “Clinical Validation Of The Endopredict Test In Node-Positive, Chemotherapy-Treated ER+/HER2− Breast Cancer Patients: Results From The GEICAM 9906 Trial“. Breast Cancer Research, vol 16, no. 2, 2014, p. R38
  8. Dubsky, Peter et al. “The Endopredict Score Provides Prognostic Information On Late Distant Metastases In ER+/HER2− Breast Cancer Patients“. British Journal Of Cancer, vol 109, no. 12, 2013, pp. 2959-2964
  9. Constantinidou, Anastasia, et al. “Clinical Validation of EndoPredict in Pre-Menopausal Women with ER-Positive, HER2-Negative Primary Breast Cancer”. Clinical Cancer Research, vol. 28, no. 20, 2022, pp. 4435–4443
  10. Penault-Llorca, Frederique et al. “Prognostic value of EndoPredict test in patients screened for UNIRAD, a UCBG randomized, double blind, phase III international trial evaluating the addition of *** (EVE) to adjuvant hormone therapy (HT) in women with high risk HR+, HER2- early breast cancer (eBC)“. SABCS 2021, PD-09-08 Spotlight Poster Discussion 9
  11. Simon, Richard et al. “Use Of Archived Specimens In Evaluation Of Prognostic And Predictive Biomarkers”. Journal Of The National Cancer Institute, vol 101, no. 21, 2009, pp. 1446-1452
  12. Vázquez-Juarez, Daniela et al. ”Follow-up of prospective cohort of Mexican premenopausal women with breast cancer who received guided adjuvant treatment with the EndoPredict assay.” SABCS 2021, P4-05-15
  13. Sparano, Joseph A. et al. “Adjuvant Chemotherapy Guided By A 21-Gene Expression Assay In Breast Cancer“. New England Journal Of Medicine, vol 379, no. 2, 2018, pp. 111-121
  14. Kalinsky, Kevin et al. “21-Gene Assay To Inform Chemotherapy Benefit In Node-Positive Breast Cancer“. New England Journal Of Medicine, vol 385, no. 25, 2021, pp. 2336-2347