Randomized trials help doctors understand if one treatment is better than the standard of care treatment for patients with breast cancer, notes Dr. Nadine Tung, M.D., Director, Cancer Risk and Prevention and Breast Medical Oncology, at Beth Israel Deaconess Medical Center. In a sit-down conversation with Susan G. Komen, Dr. Tung discusses her recently completed Komen-funded study that evaluated treatment options for breast cancer patients with inherited BRCA1/2 gene mutations.
Komen: Tell us about the INFORM Trial and what you were trying to accomplish.
Tung: To enroll in the study, a patient had to have an inherited BRCA1 or BRCA2 mutation. They had to also have newly-diagnosed HER2-negative breast cancer that was at least one and a half centimeters in size or have breast cancer that had spread to the lymph nodes. The study was comparing the effectiveness of two kinds of therapies administered before surgery (neoadjuvant); Therapy 1: a chemotherapy drug called cisplatin, and Therapy 2: the standard of care, a combination of 2 chemotherapy drugs called doxorubicin and cyclophosphamide (which we call AC). The main purpose of the study was to see if the pathologic complete response rate (pCR, when a pathologist cannot detect any remaining invasive breast cancer at surgery), was at least 20% higher using cisplatin than with the standard regimen of AC.
Komen: Why was it important to conduct this study?
Tung: There had been a prospective study (a research study conducted to discover what is likely to happen in the future) from Poland assessing cisplatin as a single treatment agent in BRCA1/2 mutation carrier patients with breast cancer. This study reported a very high (61%) pCR, which was higher than what they had reported from a retrospective analysis of the standard AC regimen. And, for women with metastatic breast cancer who had BRCA mutations, there were several studies showing that platinum chemotherapy (such as cisplatin) was more effective in treating those with the BRCA mutations than in those without BRCA mutations. There had never been a prospective study randomizing BRCA mutation carriers with newly-diagnosed breast cancer to see how the cisplatin compared to the standard chemotherapy.
Komen: How did you do things differently in your trial to see if one therapy was more effective than the other?
Tung: It’s so important to do prospective randomized trials rather than comparing data from one prospective trial with retrospective data from the past. It’s very important, when asking a clinical question, to start with the same population of patients and randomize them to one treatment or another to be able to confidently say whether one treatment is superior to the other.
Komen: What did your results show?
Tung: What we found was contrary to our expectations. We found the pathologic response was not higher in patients treated with cisplatin. The pCR was 18% with cisplatin and 26% with the AC, and this seemed to be true whether the tumor was triple negative or hormone-receptor positive. We also looked at the data to see which patients responded to treatment using a method called residual cancer burden. This is a way to ask if the tumor is completely gone or if there’s a little tumor left. If you look at the residual cancer burden, the results were the same, namely that cisplatin was not superior to the standard AC chemotherapy.
These results should not be interpreted to mean that AC is better. Our conclusion from the study is that we don’t have the evidence to say the cancer’s response to cisplatin is superior to the response to AC.
Komen: How will the results of this trial change patient care?
Tung: Our results show that the breast cancer of BRCA mutation carriers responds to DNA damaging chemotherapy in general, and not to platinum chemotherapy, specifically. Our results alleviate the need to treat every patient with a BRCA mutation and newly diagnosed breast cancer with platinum chemotherapy (such as cisplatin). Previously, many clinicians felt obligated to use platinum drugs in a BRCA-mutation carrier who had a new early stage breast cancer. Platinum drugs are certainly effective in these patients, and I think that platinum is a good option for a patient who can’t receive other chemotherapy drugs like anthracyclines (e.g. doxorubicin).
I think every step of improvement in our knowledge of breast cancer treatment has come from women participating in trials. And this is just another example. It was really the commitment of patients and their families to participate in this trial that led us to understand the role of platinum chemotherapy in this population. We now have answers that can help us optimize and personalize the treatment for breast cancer patients with inherited BRCA mutations.
You can learn more about this study in a Komen Press Release.