In the neoadjuvant setting, I generally treat locally advanced, ER-negative, HER2-positive breast cancer in a patient who desires breast conservation with TCH/lapatinib. If you consider the data, the pathologic complete response (pCR) rate for dual HER2-targeted therapies appears to be higher. Frequently, I can obtain coverage for lapatinib in combination with TCH for patients in this setting.

Answer: AC TH

It depends on the definition of locally advanced disease. If it’s T4 or N2 disease, I believe it’s reasonable to treat with a dual HER2-targeting combination with anthracycline/taxane. If the disease is not inflammatory, I would treat with AC TH. With inflammatory HER2-positive breast cancer, I would consider treatment with lapatinib or pertuzumab but would have to make a strong argument for incorporating it into the regimen so that the treatment would be covered by insurance. In the treatment of inflammatory breast cancer, no standard treatment exists because we have so few data.

For most patients with HER2-positive breast cancer, I tend to recommend the chemotherapy regimens that have been proven. My interpretation of the BCIRG 006 trial is that TCH is a perfectly reasonable regimen. It was numerically inferior to an anthracycline regimen but was associated with fewer cardiac toxicities. The data suggest that patients with HER2-positive breast cancer benefit from treatment with anthracyclines. Hence, I tend to use the AC TH regimen for younger patients or patients with higher-risk disease. For patients with lower-risk disease or those with comorbidities and high-risk disease I tend to administer TCH. Often, I’ll treat with Stephen Jones’ regimen of TCH, which contains docetaxel, cyclophosphamide and trastuzumab, because I believe that TCH with carboplatin is a difficult regimen.

Answer: AC TH + lapatinib

I would usually administer AC TH to patients with locally advanced, ER-negative, HER2-positive breast cancer who desire breast conservation. I would add lapatinib to achieve the dual HER2-targeting synergistic effect observed in several neoadjuvant trials. I chose lapatinib because I can usually obtain approval in this setting.

Answer: AC TH

In the neoadjuvant setting, for a patient such as this I generally opt for AC TH outside of a clinical trial.

Answer: AC TH or TCH

I generally approach this situation in the same way that I would in the adjuvant setting. I administer AC TH to most patients at moderate to high risk and reserve TCH for those with cardiac risk factors. The data suggest that AC TH is numerically superior to TCH, and I find it to be better tolerated.

Answer: AC TH

Our neoadjuvant regimens are identical to the adjuvant regimens. For a patient with locally advanced, HER2-positive breast cancer who desired breast conservation, I would recommend AC TH in the neoadjuvant setting.

Answer: FEC75 pac/trastuzumab

In this situation, I used to administer the Buzdar regimen of FEC75 with trastuzumab, followed by weekly paclitaxel/trastuzumab. The results of the ACOSOG-Z1041 trial, presented at ASCO 2013, showed that the concurrent administration of trastuzumab with FEC75 was not important, so I will stop that going forward. Since FEC75/trastuzumab is not superior to FEC75 followed by paclitaxel/trastuzumab, it raises an interesting question about the option of administering dose-dense AC → TH. However, the prevailing argument is that FEC75 with trastuzumab is safer for the heart than AC.

Also, the randomized TRYPHAENA trial showed similar pCR rates of about 60% to 70% when patients were assigned preoperatively to TCH with pertuzumab versus FEC followed by taxane/trastuzumab/pertuzumab. TCH/pertuzumab may become the standard toward the end of the year.

Answer: Pac + trastuzumab AC

We enroll almost all of our patients on the I-SPY 2 neoadjuvant trial investigating the benefit of adding different HER2-directed therapies or novel agents to standard neoadjuvant chemotherapy. For a patient who is not willing to be enrolled on the I-SPY 2 trial, I would opt for weekly paclitaxel and trastuzumab for 12 cycles followed by 4 cycles of AC before surgery. If the patient is elderly and can’t tolerate or refuses an anthracycline-based regimen, I would recommend TCH.