Neoadjuvant chemotherapy

Neoadjuvant therapy

The aim of neoadjuvant therapy (preoperative systemic therapy) is:

  • To enable surgery in patients in whom the cancer is too large to be operable
  • To reduce the size of the tumor in patients who are borderline for breast conservation to try to avoid a mastectomy
Neoadjuvant treatment regimens are usually similar to the adjuvant regimens used after surgery. Most are anthracycline- and taxane-based therapies with or without HER2-targeted agents. Neoadjuvant hormonal therapy can also be given in strongly ER-positive postmenopausal women who are borderline for breast conservation because of the tumor size. The value of neoadjuvnat themotherapy to assess response to chemotherapy within clinical trials, where assessment and change of chemotherapy can be implemented rapidly has been inconsistent. This point and other issue are discused in a paper suggesting that a rethink is needed for the use of neaoadjuvant chemotherapy in breast cancer - BMJ with an accompanying podcast. Full paper can be downloaed here. Unexpected outcomes. Contrary to popular expectation, randomized trials testing neoadjuvant chemotherapy have not shown an improved survival compared with postoperative adjuvant therapy. Furthermore, neoadjuvant chemotherapy was associated with poorer local control, especially when the surgery was inadequate or when it was omitted altogether because there appeared to be a complete pathological response to neoadjuvant treatment. Surgery after neoadjuvant therapy has a propensity to be inadequate, perhaps because of a patchy response within the tumor that leaves behind islands of tumor tissue, which can increase the risk of local recurrence. Also, if the tumor happens to be resistant to neoadjuvant chemotherapy then there can be a potentially detrimental delay to surgery. Even when the pathological complete response rates are high, there are still those who do not respond (20–60%). The window for an acceptable delay is much smaller for surgery (30 days) than for adjuvant chemotherapy (90 days), so the benefit of ‘earlier’ (preoperative) systemic therapy may well be overshadowed by the delay in surgical treatment in those who do not respond to the systemic therapy completely. In a meta-analysis of randomized trials, there was a 3% - 15% increased risk of locoregional recurrence in patients who received neoadjuvant chemotherapy compared with the same chemotherapy after surgery. Given these findings, the balance of risks and benefits of neoadjuvant therapy should be discussed with the patient in the informed consent process.
Newer drugs and improved regimens are being investigated with the aim of achieving better results. Some examples are given below. Human epidermal growth factor 2 (HER2)-positive and triple-negative tumors are the most chemosensitive types of breast cancer and therefore the most amenable to neoadjuvant chemotherapy. The addition of trastuzumab to primary chemotherapy has significantly improved the pathological complete response rate in HER2-positive breast cancer particularly with a combination of trastuzumab and pertuzumab with chemotherapy. However, addition of pertuzumab did not improve overall survival. Even with the best treatments, the complete response rate in triple-negative cancers is 20–45%.