Management of early breast cancer

Early breast cancer is defined as stage T1a or T1b, that is invasive cancer with a diameter of less than 10 mm.

Recent decades have seen a shift away from radical surgery for early breast cancer towards breast conserving surgery.

Survival rates are identical for patients who undergo:

• mastectomy
• lumpectomy, axillary node clearance and radiotherapy
• lumpectomy alone

Local recurrence rates are higher in patients who opt for less aggressive surgery. Rates of distant metastasis are identical.

Axillary node clearance is no longer considered to be therapeutic but it does provide prognostic information. Sentinel node biopsy predicts prognosis as accurately as total axillary clearance. The sentinel node is:

• the single axillary lymph node which drains the tumour
• identified using vital blue dye or a radioactive tracer

Further prognostic information may be obtained from examination of the bone marrow aspirated from both iliac crests.

Adjuvant therapy - hormonal and chemotherapy in early breast cancer (4):

• there is evidence that adjuvant chemotherapy, tamoxifen, and ovarian ablation or suppression substantially reduce mortality rates over 15 years in women with early breast cancer
  • standard anthracycline based polychemotherapy reduced annual breast cancer mortality by 38% in women < 50 years and by 20% in women 50-69 years - effects were independent of axillary node involvement, oestrogen-receptor (ER) and treatment with tamoxifen. Such regimens were significantly (p=0.0001 for recurrence, p<0.00001 for breast cancer mortality) more effective than cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy
  • tamoxifen for 5 years in women with ER positive disease reduced the annual breast cancer mortality rate by 31%; tamoxifen for 5 years was more effective than tamoxifen for 1 or 2 years; effects were independent of menopausal status, tumour size, patient age and lymph node involvement
    • at 15 years the absolute benefit of tamoxifen treatment was more than twice its benefits at 5 years
    • tamoxifen therapy was ineffective in women with ER negative breast cancer
  • ovarian ablation or suppression
    • led to a reduction in annual breast cancer mortality by 29% in absence of chemotherapy
• trastuzumab (Herceptin) is also effective as an adjuvant therapy in human epidermal growth factor 2 (HER2) positive early breast cancer
• more detail concerning adjuvant therapies in breast cancer is available via the linked item

Neoadjuvant treatment in breast cancer (5)

• main clinical aim of neoadjuvant (also called primary or preoperative) treatment for operable breast cancer before surgery is to downstage large cancers to reduce the need for mastectomy
  • endocrine treatments
    • evidence that aromatase inhibitors are better than tamoxifen in downstaging large oestrogen receptor positive cancers in postmenopausal women to avoid mastectomy. In particular, aromatase inhibitors may be more effective in patients with oestrogen receptor positive tumours that also strongly overexpress HER2
    • in contrast with neoadjuvant chemotherapy, pathological complete remissions are rare with endocrine therapy, but easy administration and lack of side effects make it an attractive first line option for older women with large cancers
  • chemotherapy
    • achieves clinical regression of tumours in about 70-80% of patients. This suggests that early cancers may be more chemosensitive than metastatic disease. Around 15-20% of patients achieve a complete pathological response of their tumour; this occurs more often in oestrogen receptor negative than oestrogen receptor positive tumours, and complete pathological response is a predictor for good long term outcome
  • trastuzumab
    • evidence that achieves high response rates in combination with neoadjuvant chemotherapy in breast cancers that overexpressed HER2

Notes:

• NICE (6,7) state that:
  • adjuvant therapy planning
    • with respect to postoperative assessment and adjuvant therapy planning
      • predictive factors
        • assess oestrogen receptor (ER) status of all invasive breast cancers
        • routine assessment of progesterone receptor status of tumours is not indicated
        • test human epidermal growth receptor 2 (HER2) status of all invasive breast cancers
        • ensure that the ER, PR and HER2 statuses are available and recorded at the preoperative and postoperative multidisciplinary team meetings when systemic treatment is discussed
      • offer genetic testing for BRCA1 and BRCA2 mutations to women under 50 years with triple negative breast cancer, including those with no family history of breast or ovarian cancer (6)
        
        
    • adjuvant chemotherapy for invasive breast cancer
      • for people with breast cancer where chemotherapy is indicated, offer a regimen that contains both a taxane and an anthracycline. Refer to the summaries of product characteristics for individual taxanes and anthracyclines to check for differences in licensed indications
        
        
    • adjuvant endocrine therapy for invasive breast cancer
      • tamoxifen - initial adjuvant endocrine therapy for men and premenopausal women with ER-positive invasive breast cancer
      • an aromatase inhibitor - initial adjuvant endocrine therapy for postmenopausal women with ER-positive invasive breast cancer who are at medium or high risk of disease recurrence. Offer tamoxifen to women who are at low risk of disease recurrence, or if aromatase inhibitors are not tolerated or are contraindicated
        
        
    • ovarian function suppression
      • ovarian function suppression should be considered in addition to endocrine therapy for premenopausal women with ER-positive invasive breast cancer
        
        
    • extended endocrine therapy
      • extended therapy (total duration of endocrine therapy of more than 5 years) should be offered with an aromatase inhibitor for postmenopausal women with ER-positive invasive breast cancer who are at medium or high risk of disease recurrence and who have been taking tamoxifen for 2 to 5 years
      • consider extended therapy (total duration of endocrine therapy of more than 5 years) with an aromatase inhibitor[4] for postmenopausal women with ER-positive invasive breast cancer who are at low risk of disease recurrence and who have been taking tamoxifen for 2 to 5 years
      • consider extending the duration of tamoxifen therapy for longer than 5 years for both premenopausal and postmenopausal women with ER-positive invasive breast cancer
      • endocrine therapy
      • ovarian suppression/ablation for early invasive breast cancer
        • adjuvant ovarian ablation/suppression should not be offered to premenopausal women with ER-positive early invasive breast cancer who are being treated with tamoxifen and, if indicated, chemotherapy
        • adjuvant ovarian ablation/suppression should be offered in addition to tamoxifen to premenopausal women with ER-positive early invasive breast cancer who have been offered chemotherapy but have chosen not to have it
          
          
    • biological therapy
      • offer adjuvant trastuzumab for people with T1c and above HER2-positive invasive breast cancer. Give this at 3-week intervals for 1 year in combination with surgery, chemotherapy, endocrine therapy and radiotherapy, as appropriate
      • consider adjuvant trastuzumab for people with T1a/T1b HER2-positive invasive breast cancer, taking into account any comorbidities, prognostic features and possible toxicity of chemotherapy

Reference:

1. Fisher B. et al.. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med. 1995;333: 1456-61.
2. Giuliano AE. et al.. Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg. 1995;222: 394-401.
3. Silverstein MJ. Diagnosis and treatment of early breast cancer. BMJ 1997; 314: 1736-9.
4. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687-717.
5. BMJ. 2006 Jan 28;332(7535):223-4.
6. NICE (March 2017).Early and locally advanced breast cancer - dagnosis and treatment
7. NICE (June 2023).Early and locally advanced breast cancer: diagnosis and management