Neo-adjuvant Chemotherapy For Operable Primary Breast Cancer - An Update From The Melbourne International Joint Breast Congress
Melbourne International Joint Breast Congress
I enjoyed seeing and catching up with friends. As an educational conference, it has been a good conference, and I have learnt or solidified my knowledge. And we in Wellington are doing well. Our medical oncologist and breast surgeons are up to date with their medical knowledge, and we inform and treat our patients with up to date information
As we have known for a while, there are two reasons for neo-adjuvant breast cancer treatment (where chemotherapy or endocrine therapy is given before breast surgery). One is surgical, to reduce the size of primary breast cancer to be able to perform breast-conserving surgery. The second one is oncological - to see and assess the clinical and pathological response rate in that patient to chemotherapy. Why is this oncological response important? I believe that this oncological/biological response is the most important because it gives that patient and us prognostic evidence and ability to tailor treatment (personalised medical treatment). This response is measured by looking at the histology of the resected breast cancer area. There are multiple grading systems of response to neoadjuvant therapy, but the easiest one is RCB. RCB 0 is the complete pathological response (pCR - no further cancer left), RCB 1 - minimal residual tumour left, RCB 2 - moderate residual tumour left and RCB 3 no response to treatment
Studies have found that cancer biology is important in how well they respond to chemotherapy. Her2 +ve breast cancer, as well as triple-negative breast cancer (Er-ve, Pr-ve, Her2-ve), respond the best to chemotherapy. The prognosis for patients who have achieved complete pathological response (pCR) or those whose cancer has been almost completely destroyed following chemotherapy is much better than those who do not respond to chemotherapy as well.
Should we offer any more treatment for patients who have not responded as well to neoadjuvant chemotherapy? CREATE-X trial (from Japan and South Korea) has looked at the effect of the addition of capecitabine chemotherapy in women who have not achieved good response to neoadjuvant chemotherapy. Women were randomly selected to 2 groups: one that was given capecitabine following surgery and the second group who was not given any further chemotherapy.
This trial has shown that the addition of capecitabine has led to improved disease-free survival as well as overall survival in this group of patients. This trial is well designed. Its potential issues are that these results may not apply to patients outside Japan and South Korea (probably unlikely). Occasionally there is a trial that when repeated somewhere else does not confirm these results, so it would be great if there were another trial that shows these results. And like any other chemotherapy, taking capecitabine may be associated with complications. Because of all of this, we have to inform patients of this trial, and its results and associated issues, to develop a plan of care in partnership with patients.
Patients with lobular breast cancer and patients with low-grade hormone-positive cancer (ER+/PR+ or ER+/Pr- or ER-/PR+) often do not respond well to adjuvant chemotherapy and as such is likely to be avoided.
In patients who have low-grade hormone-positive locally advanced breast cancer, would take endocrine therapy (tamoxifen vs aromatase inhibitor) before surgery help (neo-adjuvant endocrine therapy)?
What we know so far is that neo-adjuvant endocrine therapy does downstage (make primary breast cancer smaller in up to 75% of patients, but it does take time (3-6months). The often complete pathological response is not achieved. Achieving complete pathological response in this patient cohort does not appear to have the same prognostic benefit as in neo-adjuvant chemotherapy patients. IMPACT trial has shown that Aromatase inhibitors (AI) are associated with better breast conservation outcome then tamoxifen alone or combination (AI and tamoxifen), but there was no difference in survival.
Adding palbociclib to anastrozole (AI) also show promise, but results will be available later on this year at the San Antonio Breast Cancer Symposium later on this year. I am looking forward to hearing these results from my oncology colleagues who will attend this meeting.