HR+, HER2- Early Breast Cancer

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HR+, HER2- Early Breast Cancer: High-Risk Features and Recurrence Risk

Incidence of hormone receptor–positive (HR+), HER2-negative (HER2-) breast cancer

Most patients with early breast cancer (EBC) have HR+, HER2- disease. Breast cancer molecular subtypes at diagnosis includes1:

Breast icon with ALNs highlighted

Breast cancer molecular subtypes at diagnosis

  • 72.7% is HR+, HER2-
  • 12.2% is TNBC
  • 10.3% is HR+, HER+
  • 4.6% is HR-, HER2+

EBC has no spread detected beyond the breasts and lymph nodes in and around the breasts and has gone only as far as the lymph nodes in the armpit(s).2 Some patients with EBC have cancer cells that are more aggressive and more likely to grow and spread quickly, which means there is a higher risk of the cancer recurring.3,4

Five-person icon with 1.5 persons highlighted in red.

Recurrence rates

~30% of patients with high-risk, HR+, HER2- EBC may experience recurrence within 5 years, often with distant metastases.5

Sites of recurrence for patients with EBC include bone, liver, lungs, and brain.

Sites of recurrence

Most disease recurrence occurs at distant sites.

Common sites of distant recurrence include the bone, liver, lungs, and brain. Although local and regional recurrences are treated with curative intent, distant recurrences remain largely incurable but are treatable.6,7

Common sites of distant recurrence:

Some clinical features of high-risk disease

Patients with HR+, HER2- breast cancer at high risk of recurrence may present with 1-3 positive ALNs with grade 3 disease or tumor size ≥5 cm, or ≥4 positive ALNs.5 As healthcare providers, it is important to recognize the features associated with a higher risk of recurrence.

Factors associated with a high risk of early breast cancer recurrence include 1 to 3 positive ALNs with grade 3 disease or tumor size greater than or equal to 5 cm or greater than or equal to 4 positive ALNs.

EBC: clinical and pathological factors associated with a higher risk of recurrence8-10

cancer cells in a human breast.

Stage 3

Patients with stage 3 disease have a 2.0x increased risk of recurrence over 10 years vs patients with stage 1 disease

Microscope

Grade 3 disease

Patients with grade 3 disease have a 3.9x increased risk of distant recurrence over 10 years vs patients with grade 1 disease

A cluster of cancer cells being measured.

Tumor size ≥5 cm

Patients with tumor size greater than or equal to 5 cm have a 1.5x increased risk of distant recurrence over 10 years vs those with tumor size less than 5 cm in node-positive patients

Positive lymph nodes among normal lymph nodes.

≥4 Positive lymph nodes

Patients with greater than or equal to 4 positive lymph nodes have a 3.0x increased risk of recurrence over 5 years vs those with negative lymph nodes

Recurrence risk peaks at 2 years after primary diagnosis

Regardless of disease stage (stage 1, 2, or 3) or nodal status (≥4 ALNs or 1-3 ALNs), a peak in early recurrence was observed in all patients at 2 years after primary diagnosis.8,12

Graph with the risk of recurrence by stage in patients with HR+ EBC

Risk of Recurrence by Stage in Patients With HR+ EBC8

For patients with stage 1, 2, or 3 breast cancer, the curves for annual hazard rates were similar, with a steep incline at 1-2 years of follow-up.

Graph with the risk of recurrence by nodal status in patients with ER+ EBC

Risk of Recurrence by Nodal Status in Patients With ER+ EBC12

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For patients with ER+ (estrogen receptor-positive) early breast cancer, the annual hazard rates inclined and peaked between the 1- to 2-year mark for all patients with nodal involvement (≥4 ALNs and 1-3 ALNs).

ER levels of 10 fmol/mg or greater of cytosol protein based on chemical assay were classified as positive.

Doctor discussing risk of recurrence with a patient

Quantifying risk of recurrence with patients

As healthcare providers, it is important to help our patients with breast cancer have a quantitative understanding of their risk of recurrence over the course of their treatment journey.

Knowledge on disease prognosis may help patients adjust expectations, boost treatment adherence, and increase involvement in shared decision-making.13

Downloadable PDFs

INFOGRAPHIC: High-risk HR+, HER2- EBC Prognosis and Risk of Recurrence (PDF)

INFOGRAPHIC: High-Risk, Early Breast Cancer: Risk of Recurrence and the Importance of Quantifying Risk (PDF)

https://main--lusa-lillymeded-aem-us--elilillyco.aem.page/medical/fragments/figure-captions/high-risk-features-page-video1

Clinicopathologic features of early vs late recurrence of HR+, HER2- EBC

Dr. O’Shaughnessy elaborates on the spectrum of high-risk HR+, HER2- early breast cancer and discusses the clinicopathologic features associated with early and late recurrence.

https://main--lusa-lillymeded-aem-us--elilillyco.aem.page/medical/fragments/figure-captions/high-risk-features-page-video2

Understanding the risk of recurrence of HR+, HER2- EBC

Dr. O’Shaughnessy shares how she communicates risk of recurrence to her patients with HR+, HER2- early breast cancer patients who may be at high risk.

https://main--lusa-lillymeded-aem-us--elilillyco.aem.page/medical/fragments/figure-captions/high-risk-features-page-video3

Communicating the quantitative risk for recurrence of HR+, HER2- early breast cancer

Dr. O’Shaughnessy elaborates on her approach on setting expectations and quantifying risk of recurrence for patients with HR+, HER2-, early breast cancer at a high risk for recurrence.

References

  1. Howlader N, et al. J Natl Cancer Inst. 2014;106(5):dju055.
  2. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/early-stage-breast-cancer. (Accessed January 29, 2024).
  3. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/recurrent-cancer. (Accessed January 29, 2024).
  4. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/aggressive. (Accessed January 29, 2024).
  5. Sheffield KM, et al. Future Oncol. 2022;18(21):2667-2682.
  6. Gerber B, et al. Dtsch Arztebl Int. 2010;107(6):85-89.
  7. Cardoso F, et al. Ann Oncol. 2020;31(12):1623-1649.
  8. Cheng L, et al. Cancer Epidemiol Biomarkers Prev. 2012;21(5):800-809.
  9. Holleczek B, et al. BMC Cancer. 2019;19(1):520.
  10. Pan H, et al. N Engl J Med. 2017;377(19):1836-1846.
  11. Brown J, et. al. Poster presented at: SABCS 2019. Poster P5-08-18.
  12. Colleoni M, et al. J Clin Oncol. 2016;34(9):927-935.
  13. Ciria-Suarez L, et al. Front Psychol. 2020;11:540083.

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