Recommendations for breast cancer therapies

The Breast Quality Audit of Australia and New Zealand has undergone a refresh to help clinicians stay up to date with contemporary recommendations for breast cancer therapies.

International efforts to improve outcomes for patients with breast cancer has resulted in a deluge of information from clinical trials and resulting changes in practice that can be overwhelming for clinicians to keep up with.

Dominating these advances is the transition in use of chemotherapy and immunotherapy to the neoadjuvant, or pre-surgery treatment period, from use in the adjuvant post-surgery treatment period.

In May 2023, the breast quality audit of Australia and New Zealand, the BreastSurgANZ Quality Audit (BQA), rolled out an updated set of data fields to accurately capture the use of neoadjuvant chemotherapy (NACT) and immunotherapy by clinicians in Australia and New Zealand.

In addition, the BQA platform now provides individual clinicians with a real-time dashboard of their own practice compared with the national average practice in attainment of quality standards in breast cancer care.

This is revolutionary in allowing clinicians to review individual practice and identify areas in practice that might need improvement.

Quality in breast cancer care encompasses not only surgery but appropriate use of adjuvant therapies such as radiation, chemotherapy and immunotherapy (here).

It has long been recognised that patients who are managed by multidisciplinary teams have better uptake of adjuvant therapies and improved survival and recurrence outcomes, as well as appropriate access to clinical trials.

The BQA captures surgical interventions, use of multidisciplinary case discussion, and treatments recommended and used.

The importance of neoadjuvant systemic therapy in breast cancer

Currently, there are six described biological types of breast cancer that respond differently to systemic therapies (here).

These are based on the presence or absence of oestrogen receptors, progesterone receptors, human epidermal growth factor receptor 2 (HER2), and how rapidly the cancer cells are multiplying (Ki67).

The greatest benefits of neoadjuvant systemic therapies are seen in stage II–III triple negative breast cancer and HER2-positive breast cancers (HER2+), but benefit is also seen if Ki67 is greater than 20% regardless of the receptor status.

The benefit of neoadjuvant systemic therapy (NST) includes tumour downstaging to enable surgical resection of previously irresectable tumours, improved rates of breast-conserving surgery, and avoidance of axillary dissection surgery in selected women with preservation of limb function and reduced risk of lymphoedema. In patients who are at high risk for genetic mutation, the use of NACT provides time for germ-line mutation analysis for BRCA1/2, PALB2, or TP53, and, if these are present, allows adaptation of surgical management to prophylactic mastectomy.

Importantly, NST allows prognostication on the basis of clinical response. After surgical resection, the tumour is microscopically assessed to determine the systemic therapy’s effectiveness. Patients with tumours that are successfully treated by NST and achieve a complete pathological response have an increased overall survival and do not benefit further from adjuvant therapy. Conversely, patients with tumours that are only incompletely treated by NST can achieve an improvement in overall survival through additional treatment with tailored adjuvant therapies.

Triple negative breast cancer is considered an aggressive but more chemosensitive biological subtype of breast cancer. Treatment of triple negative breast cancer with NACT can result in complete pathological response in up to 45% of patients, and addition of the monoclonal antibody pembrolizumab to a platin/anthracycline-based chemotherapy regimen achieves complete pathological response as high as 60% and generates a trend toward improved event-free survival. Patients with residual tumour are identified for treatment with capecitabine to increase disease-free survival by 13% and overall survival by 8%.

HER2 positivity also confers aggressive biology but allows treatment with HER2-targeting immunotherapy. Adding the immunotherapy agents trastuzumab and/or pertuzumab to standard chemotherapy in stage I–III HER2+ tumours further improves the rates of complete pathological response, reduces disease recurrence and improve overall survival from 20% to 40%. Patients with complete pathological response continue treatment with trastuzumab, but patients with residual tumour are identified for alternate adjuvant treatment with trastuzumab–emtansine (T-DM1) to increase disease-free survival by 10–88.3%.

Accordingly, both the 2019 St Gallen International Consensus Guidelines for the primary therapy of early breast cancer and the 2021 ASCO guideline Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer state that NST are now considered the preferred initial approach, and should be offered to all women with stage II or III triple negative breast cancer or HER2+ breast cancer. The ASCO guidelines are available to download to your phone as an application (app) or Pocket Cards.

A snapshot of neoadjuvant systemic therapy use in Australia and New Zealand

The most recent assessment of use of NST in Australia and New Zealand is from BQA data that immediately precede publication of the 2019 St Gallen International Consensus Guidelines, the 2021 ASCO Guideline, and the coronavirus disease 2019 (COVID-19) pandemic. These data from 116 745 patients entered to the BQA showed that, in the ten years leading up to 2019, the use of NACT increased around 26% per year from very low levels to a total of 32% of patients with triple negative breast cancer and 35% of patients with HER2+ breast cancer. In patients with HER2+ breast cancer, neoadjuvant trastuzumab was used 30% of the time.

Clinicians must of course consider the appropriateness of systemic therapy for individual patients. In patients who are older or who have comorbid conditions that may be affected by treatment side effects, such as cardiac problems in patients treated with trastuzumab, the risk of treatment might outweigh the benefit. Some patients may not accept systemic therapies due to personal preferences or travel distance to treatment centres.

The BQA strongly endorses appropriate evidence-based use of NACT and has therefore updated the key performance indicator for its use in women aged under 70 with triple negative or Her2+ tumours to >70%.

An early snapshot of the new BQA data encompassing patients diagnosed from the start of 2018 to July 2023 has shown that Australian and New Zealand clinicians are achieving a rate of 39% (personal communication MB).

Clinicians, and especially breast surgeons, can therefore strive further to identify patients that would benefit from both adjuvant and neoadjuvant therapies. Surgeons need to be aware of changes in chemotherapy practice and routinely refer patients with breast cancer for multidisciplinary team discussion and consideration of all adjuvant and neoadjuvant therapies. Familiarity with the evidence for use of NST can aid with counselling of patients with breast cancer regarding the sequence of therapies with the greatest benefit to them as individuals.

Members of the Breast Surgeons of Australia and New Zealand are thanked for their diligence in entering treatment data to the BQA. Following this recent launch of the updated BQA platform with real-time clinician feedback, the BQA will be primed to further evaluate the use and effectiveness of NACT in treatment of breast cancer in Australia and New Zealand, to identify barriers to treatment success, and make recommendations for innovative future improvements in care.

Dr Jaime Duffield is Senior Clinical Lecturer at the University of Adelaide.

Dr Melissa Bochner is the Chair of the Breast Quality Audit Steering Committee, Breast Surgeons of Australia and New Zealand.

The statements and opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the Breast Surgeons of Australia and New Zealand, the Australia Medical Association, the MJA or InSight+ unless so stated.

Disclosure statements:

There are no financial conflicts of interest to disclose.

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

The work described has not been published previously. Components of this manuscript were published as an abstract and a podium presentation at the 2022 Royal Australian College of Surgeons Annual Scientific Conference, Brisbane, Australia, 2–6 May 2022.

The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated. 

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