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HR+, HER2- Early Breast Cancer

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High-Risk Features

High-Risk Patient ID

Clinical Trials

Adherence and Support

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
chevron-filled-down Image description

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


Recurrence rates

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

Five-person icon with 1.5 persons highlighted in red.

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:

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

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 EBC.
chevron-filled-down Image description

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

Stage 3

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

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

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

≥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


Risk of Recurrence by Stage in Patients With HR+ EBC8

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

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.

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

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

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

Related Resources

Downloadable PDFs

Download PDF Medical Answer PDF Document Created with Sketch. INFOGRAPHIC: High-risk HR+, HER2- EBC Prognosis and Risk of Recurrence
Download PDF Medical Answer PDF Document Created with Sketch. INFOGRAPHIC: High-Risk, Early Breast Cancer: Risk of Recurrence and the Importance of Quantifying Risk


Hormone receptor positive, HER2 negative is a real spectrum disorder, there is a lot of heterogeneity and gradation of biology, and the highest risk with the patients really come in 2 flavours, one is the group of patients at risk for early recurrence. These are patients with larger tumours, higher nodal burden and generally higher grade, higher proliferation, as well as high genomic signature, 21 gene recurrence score, 70 gene signature. However, there is a second group of patients there at high risk for late recurrence. These patients also generally have breast cancers with higher tumour burden, higher tumour size, a higher nodal status, and generally can also be somewhat higher grade, somewhat more higher proliferative, but these patients remain at risk for decades. And some of those, indeed, will be indolent, but they just have a lot of high tumour burden. So, there is a spectrum of a definition of high-risk disease.

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.


For women at high risk of recurrence of breast cancer it is very important for them to have a very solid understanding of what that risk is. What is their approximate quantitative risk of recurrence of breast cancer? Because that really helps them understand why we are asking them to take treatment that does have toxicity – chemotherapy, endocrine therapy, targeted therapies – for their early-stage breast cancer in addition, of course, to loco-regional treatment. But it is very important then in the context of what the benefits are from the therapies for them to understand the risks. And then, together to work to make sure that they can tolerate the therapies and get the best possible outcome.

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.


For women at high risk of recurrence from their HR positive, HER2 negative breast cancer, I think, it is very important for them to have a quantitative understanding of what their risk of recurrence is over the first 5 years and over their lifetime. And then we want to offer them, of course, every proven treatment to decrease that risk of recurrence. I think it is very important to frame this initially, when you are first meeting a patient, and walk through what the treatment plan will be, giving them a quantitative understanding of exactly how much benefit – what is the reduction risk of recurrence they get? – every step along the way. And women really want to get as low on the risk of recurrence as possible, of course. If you meet a patient who is midstream in her therapy, again, you can say, well, you had this treatment here, this is my estimation of what your residual risk of recurrence is, and here is what I recommend. Let’s go through this step-by-step processing what we can do given the proven clinical trial data to reduce your risk of recurrence. And I write it down, and I think it is very helpful to be as quantitative as possible in telling that story.

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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