Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. The Cochrane Breast Cancer Group have published reviews on more than 80 topics, and these were added to in September 2023 with a review of platinum-based chemotherapy for women with early stage triple negative breast cancer. In this podcast, Rachel Dear, co-author and breast cancer oncologist based in Sydney, talks with lead author, Sofia Mason from the Garvan Institute of Medical Research in Darlinghurst Australia about the findings.

Rachel: Hi Sofia, perhaps we could start with some background, what's triple negative breast cancer and what's platinum-based chemotherapy

Sofia: Hi Rachel. Triple‐negative breast cancer is an aggressive subtype of breast cancer. In early triple-negative breast cancer, chemotherapy is used before or after surgery to reduce the chances of cancer coming back. One type of chemotherapy, platinum chemotherapy, has been shown to improve the likelihood of the cancer in the breast disappearing when it's used before surgery. But, there's uncertainty about long-term outcomes, such as whether it prolongs the time to cancer relapse or leads to a longer life.

Rachel: Thanks. It's definitely important to understand more about these outcomes, and I know that the use of platinum chemotherapy varies quite a bit across the world, which I realise is why you did this review. Could you tell us some more about the aims of the review?

Sofia: To state it formally, our main question was: does platinum‐based chemotherapy, used before or after surgery in people with early triple negative breast cancer, lead to longer disease-free survival and overall survival? We also wanted to explore the side effects of platinum chemotherapy, and negative outcomes such as treatment delays, dose reductions and death associated with treatment; and to look at the effects for different subgroups.

Rachel: Ok, great! What kind of studies did you find?

Sofia: We found 20 studies that involved just under 4700 people with early triple‐negative breast cancer, with average follow‐up ranging from three to eight years. Sixteen of the studies used chemotherapy before surgery (which we call 'neoadjuvant') and four studied adjuvant chemotherapy which is used after surgery. Most used the platinum drug carboplatin, and this was the drug used in all the studies that reported long-term outcomes.

Rachel: Yes, it seems like carboplatin is the drug I've seen used most often clinically. So, was there a benefit in your primary outcomes?

Sofia: Yes! Carboplatin chemotherapy was associated with improvements in both disease‐free survival and overall survival, reducing the chance of disease recurrence and death by about one third. We saw these benefits with neoadjuvant or adjuvant chemo, and there was also a benefit in pathological complete response which aligns with previous research.

Rachel: Interesting! What about the subgroup analysis – was there any particular group that benefitted?

Sofia: No, we didn't find that any particular group, such as people with the high risk breast cancer gene BRCA, or where the cancer had spread to their lymph nodes, had more benefit from platinum chemotherapy. We also saw a benefit regardless of whether or not the intervention arm contained anthracycline chemotherapy.

Rachel: Ok. Let's talk a bit more about the negatives – what did you find?

Sofia: People receiving platinum chemotherapy were more likely to have chemotherapy dose reductions or delays, or stop chemotherapy early. Platinum chemotherapy also caused more serious side effects including anaemia, neutropaenia and thrombocytopaenia. However, it was not associated with an increase in febrile neutropenia or neuropathy and death caused by treatment was very rare, with no difference between the platinum and the non-platinum groups.

Rachel: And in regard to the negatives for the review itself, what would you say are its limitations?

Sofia: First a positive: the evidence was generally of high quality and enough to answer our main questions. The main issue to me is that the chemotherapy protocols varied quite a lot across studies, and as a result, we don't know exactly what the best combination of chemotherapy is. On this note, it's challenging to know how to apply our findings when emerging therapies, like immune and targeted therapies, are added to the chemotherapy.
Additionally, we were unable to capture and report on outcomes at the level of age, gender, culture or race. As most of these trials took place in the US, Asia or Europe, Black or African, Pacific Islander and Indigenous people are likely to be under-represented. We were also disappointed that none of the studies reported quality of life, which we had initially set out to measure and record. Hopefully, more recent trials will be designed with these things in mind and we'll be able to look at them in updates of the review.

Rachel: Agreed! Ok, so, for now, would it be fair to say that the take home message from the review is that carboplatin chemotherapy improves overall and disease free survival for people with early triple negative breast cancer, but at the cost of more haematological toxicity, treatment delays and dose reductions.

Sofia: Exactly!

Rachel: Great. Thanks very much for talking to me about the review and, finally, where can people find it?

Sofia: Thanks Rachel. The review's published on cochrane library dot com – search for 'platinum-based chemotherapy for early breast cancer' and it will come up.