Breast cancer: the benefits of neo-adjuvant therapy
Posted on 30 October 2018
Treating the behaviour of breast tumours with neo-adjuvant systemic therapy – a first step therapy to shrink a tumour before the main treatment (usually surgery) – is replacing the old-school approach of cutting first and asking questions later.
As Dr Rika Pienaar, an oncologist specialising in the treatment of breast cancer at Mediclinic Panorama, says, to move a breast tumour back in terms of time, you need systemic neo-adjuvant therapy. “Although there is no difference in survival, there are improved benefits for the patient when adopting this approach,” she says.
Another pivotal change in the management of breast cancer over the past few years is the understanding that patients shouldn’t be seen in isolation – but rather by a multi-disciplinary team. “An oncologist, surgeon, reconstructive surgeon and occasionally a radiologist and geneticist should weigh in on the optimal sequence of treatment.” Once the team understands the biology and behaviour of the tumour, they can downscale surgery and treatment.
“Traditionally, if the tumour was operable, the surgeon would remove the tumour and then refer the patient to the oncologist, who often would not even have seen the extent of the initial tumour,” she says.
“When we first looked at neo-adjuvant therapy in the 1990s, we knew it wasn’t going to change survival rates, but that it was going to downstage the breast in an operable situation,” says Dr Pienaar. “Now the indication for neo-adjuvant is a bit different. Yes, it will downstage the breast (reduce the need for extensive surgery) but it will also downstage the axilla.”
As Dr Pienaar adds, the risk of lymphedema after surgery is 15 to 20% and when coupled with radiotherapy, that percentage swings up to 45%. Lymphedema also carries with it high morbidity risks and a lifetime of problems.
“In the old days, if doctors felt a lymph gland, an axillary clearance would follow. These days, we perform neo-adjuvant therapy, which can then be followed by a sentinel lymph node biopsy to ascertain whether surgery is needed. Axilla is now well-treated with radiotherapy instead of surgery.”
Dr Pienaar cites more than nine trials where neo-adjuvant chemotherapy has been compared against adjuvant treatment using the same combination of chemotherapy. The largest of these trials was the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 trial, which included 1523 patients with T1-3N0-1M0 breast cancers.
Four randomised cycles of cyclophosphamide and doxorubicin were given to a group of 1523 patients with early-stage breast cancer, i.e. some received chemotherapy pre- and some post-surgery. In the group that received neo-adjuvant therapy, there was an 80% clinical response rate (CRR) – 30% of whom displayed a complete clinical response (cCR), and the breast conservation therapy rate was higher among the neo-adjuvant patients (67%) compared to the adjuvant group (60%).
Based on the trials, the neo-adjuvant patients were also more likely to have negative axillary lymph nodes at the time of surgery when compared to the adjuvant group. The definitive results of the trials indicated the potential of neo-adjuvant therapy to downstage the disease and facilitate breast conservation therapy, but also to decrease morbidity that was associated with axillary surgery.
The subtype of cancer also plays a significant role when it comes to deciding whether to apply neo-adjuvant therapy. With HER2/fish positive and Basal-like (or triple negative) type tumours, neo-adjuvant therapy plays an important role. “It’s a way to measure response, and if there is residual disease, it leaves us with something that we can evaluate for a target for subsequent adjuvant therapy,” Dr Pienaar explains.
As she further explains, the outcome in those tumours is much better than the old days because there is no longer a “one-shoe-fits-all approach”. Doctors can now tailor treatment according to the response and do genomic testing on the residual tumour for more specific treatment to target.
Neo-adjuvant therapy is also helpful when young patients need to undergo genetic testing to determine whether bilateral surgery is required. “As it can take up to three months to run these gene tests, chemotherapy can be applied in the interim and doctors can make better surgical decisions once they have the gene results,” she explains. In the elderly, hormonal neo-adjuvant therapy is a more gentle approach.
In short, there is a clear movement away from extensive surgery when it comes to the treatment of breast cancer. As Dr Pienaar states, “Systemic neo-adjuvant therapy is enhancing the outcome for the patient if it’s done in the right sequence.”