By Karuna Jaggar, Executive Director
Susan Love says “Surgery is a dying art. Which is great since surgery is a last resort.”
But for many years, before radiology departments took over these tasks, surgeons did breast biopsies and delivered the news about a breast cancer diagnosis. And then surgeons did what they do best: cut out the cancer.
Some researchers and doctors have even begun to say that certain breast cancers “aren’t surgical diseases.” Instead it’s systemic therapies, and even sometimes radiotherapy, that are most effective treatments for some breast cancers.
Indeed, over the last 10 years it is increasingly common to give triple negative and sometimes HER2+ breast cancer patients systemic therapies before surgery. Chemotherapy before surgery can dramatically shrink triple negative breast cancers, until sometimes they aren’t even detectable. And a combination of trastuzumab (Herceptin) and pertuzumab (Perjeta) can be very effective for HER2-positive tumors.
Pathological complete response (pCR) is the lack of all signs of cancer in tissue samples that are removed during surgery or biopsy after systemic therapy. Knowing if the cancer achieves pCR helps predict how well the treatment will work and if the cancer will come back. Besides predicting outcomes and assessing the efficacy of treatments, neoadjuvant treatment can downsize tumors resulting in less extensive surgery.
Patients with hormone positive breast cancer, on the other hand, are rarely given neoadjuvant treatment. One of the reasons is that neoadjuvant hormone therapy rarely produces pCR, perhaps because hormone therapy needs more time to work. Another reason is that pCR is not predictive for hormone positive disease, in the way it is for hormone negative disease. Eric Winer notes the paradox that the better the prognosis, the less likely neoadjuvant treatment will eradicate cancer.
But there are clinicians and researchers who are interested in using neoadjuvant hormone therapy. Indeed, the second plenary lecture at SABCS on Thursday by Dr. Ingrid Mayer (Vanderbilt) focused on this issue and was titled “Neoadjuvant Endocrine Therapy: The Times They are A-Changing.”
This talk focused on potential markers for hormone positive breast cancers, since pCR isn’t predictive for these cancers. And Dr. Mayer proposed that the Preoperative Endocrine Prognostic Index (PEPI) score and Ki67 are useful biomarkers that are ready for use, in addition to possible genomic signatures in development. Dr. Mayer concluded her talk hoping to see Ki67 and PEPI used to support accelerated approval of hormone targeted therapy combinations, for drugs that cause apoptosis vs proliferation arrest.
The POETIC study is the largest (4,486) study on neoadjuvant hormone therapy and shows that Ki67 can be predictive of outcomes. Patients with low Ki67 at the start of the study had good outcome compared to patients with high Ki67 that stayed high, who did poorly. Interestingly, those patients with high Ki67 at baseline that was lowered at 2 weeks had good outcome, almost as good as those who started with low Ki67. Given Ki67’s predictive abilities at just 2 weeks, there is interest in using it to select therapy, so come patients can avoid chemo while others get it. It’s even been suggested by Dr. Winer that POETIC is a cheap and available alternative when genomic assays (like OncotypeDX) aren’t available to help determine the best frontline treatment.
Eric Winer’s McGuire Memorial Award lecture posed the provocative question: “Does all early breast cancer need surgery?” Surgery comes with a lot of complications that would be wonderful to avoid in some selected patients. Dr. Winer notes that early stage ER+ breast cancer patients who did not get surgery have no difference in survival and metastasis free survival after 12 years, although there are some additional local recurrences.
Patients can sometimes feel nervous about reducing treatment, especially given the fact that half of hormone positive breast cancers that recur do so after five years (so-called “late recurrence”). We do need better treatments, but we don’t need treatments that aren’t helping.