Historically, neoadjuvant chemotherapy (chemotherapy before surgery) was only offered to patients with locally advanced breast cancer (large, node positive, skin involvement or inoperable) or inflammatory breast cancer. However it is now more common for patients to undergo systemic therapy (chemotherapy) first even if they have operable or have early stage breast cancer.
In some cases, neoadjuvant therapy is given to reduce the size of the tumour because it is either too big to remove surgically or a reduction in size of the tumour with the chemotherapy will make it easier to perform breast conservation surgery and the surgeon could convert the initial proposed plan of a mastectomy to breast conservation.
Other indications for its use include- women who have inflammatory or inoperable breast cancer, in order to reduce the size of the tumour so that a smaller amount of tissue can be removed to improve cosmetic result, to give patients time to undergo genetic testing if they have a strong family history of breast cancer such that they may be able to proceed to a bilateral skin-sparing mastectomy at completion of the chemotherapy. It may also be used to observe the effectiveness of the treatment; to give information about the prognosis of the cancer.
In pregnancy, it may give time to allow the pregnancy to proceed and for the baby to be delivered safely before proceeding to the surgery.
Neoadjuvant chemotherapy offers a chance to destroy any cancer cell that may have already spread from the breast to the rest of the body as well as acting on the breast cancer in the breast itself.
Patients who have hormone receptor positive breast cancers may also be offered neoadjuvant hormonal therapy.
Clinical trials have demonstrated the use of neoadjuvant chemotherapy is equivalent to adjuvant therapy in terms of overall survival. It also increases the likelihood that breast conserving surgery will be successful. Thus while it does not prolong survival it may reduce the need for mastectomy and therefore reduces surgical morbidity without increasing the risk of locoregional recurrence (recurrence in the breast or lymph nodes).
A meta-analysis of nine randomised studies comparing 3946 patients found no significant survival difference between patients who received neoadjuvant chemotherapy verses those that received adjuvant chemotherapy.
The benefits of neoadjuvant chemotherapy include the increased ability to perform breast conserving surgery and a reduced need for axillary lymph node dissection. A meta-analysis of 14 prospective randomised trials of neoadjuvant verses adjuvant chemotherapy in 5500 patients with breast cancer revealed that neoadjuvant chemotherapy was associated with a 16.6 percent decrease in mastectomy rate (eg- more patients were able to maintain their breasts and have residual tumor removed with a lumpectomy with neoadjuvant chemotherapy).
After neoadjuvant chemotherapy surgery is undertaken, the pathological assessment of the tumor will determine how effective the chemotherapy has been. The residual cancer burden correlates with disease-free survival outcomes. If there is a complete pathological response (eg- no further tumor seen after surgery) this is a powerful prognostic factor.
A complete pathological response is more likely seen in patients that have high grade ER negative and or HER-2 positive breast cancers compared to those that have low grade ER positive tumors.
While neoadjuvant chemotherapy can have advantages, it is not for every patient. Some patients may feel uncomfortable knowing the breast cancer is still in their body and therefore they may prefer to have surgery upfront. They may also be anxious knowing that the breast cancer could be growing during the treatment. Careful follow up examinations and imaging are always planned by the surgeon if a patient opts to undergo neoadjuvant chemotherapy. There are a number of pros and cons which need to be discussed with the breast cancer surgeon.