Identification of High-Risk Early Breast Cancer

 

 

Figure 1: Consensus algorithm for the management of patients with HR-positive, HER2-negative early breast cancer at high risk of recurrence

Background

• Globally in 2020, 2.3 million women were diagnosed with breast cancer and 685,000 women died of breast cancer:^[3]

  • survival rates have improved in recent years, with almost 90% of women diagnosed with breast cancer surviving for ≥5 years after diagnosis^[4]

  • accordingly, by the end of 2020, 7.8 million women diagnosed with breast cancer in the past 5 years were alive, making it the world’s most prevalent cancer.^[3]

• More than 90% of patients with breast cancer are diagnosed early and are potentially curable with highly effective modern treatments^[3–5]

  • approximately 70% of these patients have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (Table 1)^[3,5,6]

  • the goal of treatment for these patients is to optimise disease free survival and overall survival by preventing early recurrence and development of metastases while maintaining quality of life and avoiding long-term sequelae^[5,6]

  • standard treatment varies depending on the risk of recurrence but includes combinations of:^[3,5,6]

    • surgery

    • radiotherapy

    • neoadjuvant (before surgery)/adjuvant (after surgery) chemotherapy

    • adjuvant endocrine therapy

      • standard endocrine therapies such as tamoxifen or aromatase inhibitors, which are taken for 5–10 years, are the cornerstone of adjuvant treatment because they significantly reduce the risk of breast cancer recurrence and mortality in these patients.^[3,6,7]

• Most patients with HR-positive, HER2-negative early breast cancer do not experience recurrence on standard care, but up to 30% of those with high-risk clinical and/or pathological features may develop distant disease recurrence in the first 10 years:^[5,6]

  • recent developments have been achieved in identification of patients at increased risk of recurrence and in treatments to decrease this risk (Table 2)^[6]

  • an expert group developed a consensus treatment algorithm to help healthcare professionals with an interest in oncology manage patients with HR-positive, HER2-negative early breast cancer at high risk of recurrence (Figure 1).

Table 1: Relevant characteristics of breast cancer and scoring systems

Table 2: Adjuvant treatments for early breast cancer^[13,14]

Management of patients with HR-positive, HER2-negative, early breast cancer

Prior to initial treatment

• Consider germline BRCA testing in patients presenting with HR-positive, HER2-negative early breast cancer with a family history or other high-risk criteria for genetic susceptibility, in line with national or European Society for Medical Oncology (ESMO) guidelines.^[1] An update to the ESMO guideline is due to be published late 2023, this information was correct at time of publication.

• Assess risk of recurrence prior to deciding on the choice of:

  • primary surgery

  • neoadjuvant chemotherapy followed by surgery

    • different factors, which vary between individual patients, should be considered when assessing the risk of recurrence (Box 1 (see figure 1))

• Consider short preoperative endocrine therapy for endocrine sensitivity assessment.

Following initial treatment

Primary surgery

• Reassess the risk of recurrence postoperatively (Box 1)

• Recommend chemotherapy according to risk

• If the patient meets OlympiA trial criteria,^[2] BRCA testing (if not previously done) should be performed to consider adjuvant Olaparib.

Neoadjuvant chemotherapy/surgery

• Patients who have received neoadjuvant treatment (chemotherapy or endocrine therapy) prior to definitive breast surgery should be classified according to their response. Patient risk should be evaluated according to (prior to any systemic therapy):

  • Ki67 index ≥20% (Table 2) as determined by the investigational assay at a designated central laboratory

    • test should be performed on tumour tissue from the initial diagnostic biopsy

  • high histologic/nuclear grade 3 as defined by the Bloom-Richardson grading system

    • test should be performed on tumour tissue from the initial diagnostic biopsy

  • primary tumour size ≥5 cm on breast imaging – for example, mammogram, ultrasound, or magnetic resonance imaging (MRI)

  • axillary lymph node involvement

• Assess response using the Clinical-Pathologic Scoring System incorporating ER status and nuclear grade (CPS+EG) or preoperative endocrine prognostic index (PEPI) scoring systems

• If the patient meets OlympiA trial criteria,^[2] BRCA testing (if not previously done) should be performed to consider adjuvant Olaparib.

Adjuvant endocrine therapy

• HR-positive patients should receive standard adjuvant endocrine therapy for 5–10 years

• When indicated, abemaciclib and olaparib are given in addition to standard adjuvant endocrine therapy

• In individual patients, both abemaciclib and olaparib may be indicated. At the time of writing the optimal management and sequencing strategy for HR-positive cases with BRCA1-2 germline mutations remain controversial

• The indication of abemaciclib or olaparib is based on the TNM staging system (Table 3) and Ki67 index (Table 2) and should follow the inclusion criteria of the monarchE and OlympiA trials.

• It is not recommended to use both agents (abemaciclib and olaparib) concomitantly.

Table 3: TNM staging of breast cancer^[16]

Acknowledgement: Jemma Lough, independent medical writer, helped draft this article.

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Lead Image: crystal light/Shutterstock

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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: Identification of High-Risk Early Breast Cancer - Medscape - Aug 01, 2023.