When, if ever, do you consider administering weekly paclitaxel prior to dose dense AC for neoadjuvant treatment of breast cancer?

There are data that the sequence of initiating neoadjuvant chemotherapy with a taxane prior to an anthracycline may result in greater reduction of circulating breast cancer cells (Pachmann 2004 - page S224). In the small randomized NeoSAMBA trial, T-FAC had improved clinical outcomes, such as DFS, compared to FAC-T (n=118, Bines 2018). However, in a recent Cochrane review, including 1,415 patients in 5 neoadjuvant trials, there was no difference in endpoints such as pCR and DFS in those who received a taxane vs. an anthracycline first (Zaheed 2019). In a number of research studies, including various arms within ISPY-2, investigational agents are often given along with a taxane, followed by AC alone. In summary, at this time, there are no po...

In HER2-negative disease, I routinely administer the taxane first, followed by AC in the neoadjuvant setting. As others have pointed out, there are no strong data suggesting that long-term outcomes (DFS or OS) are different with either sequence. However, the Neo-tAnGo study suggested improved pCR rates with taxanes first. As Dr. Kalinsky mentions above, the recent Cochrane review by Zaheed et al did not find differences in endpoints. I would point out that of the studies assessing pCR, Neo-tAnGo was the largest, and that the second largest study (ACOSOG Z1041), which found no differences by sequence, was focused in HER2-positive disease. With the data in HER2-positive breast cancer showing that anthracyclines add little benefit in the era o...

I have reversed the order in the neoadjuvant setting if clinically I was more worried about AC toxicity and want to see how much I can get from weekly taxol. An older, frail patient with unoperated on triple negative disease, significant comorbodities, risk of caxiotoxicities otherwise, would make me more inclined to reverse the order. This is largely an individual patient judgement and not based on particular data.