Dual HER2-Targeted Neoadjuvant Therapy for BC

Hope S. Rugo, MD:So, for this patient, I have a really frank conversation with her, and she wants to avoid the anthracycline. I think with anER-negativeHER2-positive breast cancer like this, we’re OK starting with TCHP. A lot of these patients have a very rapid response, so by the time they come back for their next docetaxel 3 weeks later, we can’t even feel the mass. And we use growth factors routinely, usually a long-acting myeloid growth factor—now that you can actually put that on the skin before they leave the infusion center—and it self-injects 24 hours later. That has made it much easier for patients, and they only have to come in for a treatment every 3 weeks. So, growth factor plus that chemotherapy works pretty well.

My experience with this regimen is that people do get more diarrhea with it, with pertuzumab, and there is some nausea associated with the carboplatin. You can get neuropathy as well, although it’s not as common. So, we do a lot to try and support the patients and check in on them as well to make sure they can get through their treatment cycle.

When we’re thinking about double antibody therapy, when you haven’t done a randomized study or you did a blinded study and you’re giving it anecdotally in your clinic, it’s hard to know how much better it is than giving trastuzumab alone. But we have a sense that it’s overall better, which agrees with a number of studies, because we have so many patients having pathologic complete responses who haveHER2-positive disease. My experience with this is that people respond well. In terms of tolerating it, it does cause diarrhea. So, having a proactive approach really makes a big difference. I’ve had a couple of patients get a sun-induced rash, but we can generally manage that fairly well with steroids. And then if people are getting TCH, I really do a strong education about diarrhea because it can be such a big deal for them.

This patient has hormone receptor-negativeHER2-positive disease. And if she has no residual invasive cancer at the time of surgery, so-called R1, I would feel very comfortable that she had had an excellent response and had a good prognosis. Based on the data that we have now, we would continue trastuzumab to complete a year. We wouldn’t continue pertuzumab because it’s not yet FDA approved for that and it’s very expensive, so insurers are very cautious about having you give the drug. And we, of course, don’t know how long you need to take pertuzumab to see a beneficial effect. But hopefully, we’ll see that in the not-too-distant future and we’ll begin to study that more.

One other thing I bring up with patients when they come in like this—and it’s all kind of overwhelming—is the support networks and how important they are for the patient. And then we talk about scalp cooling, which is also really important for a working woman in particular, but even our older patients who really appreciate the opportunity to use scalp cooling. We know that with the TCHP regimen, and that’s one reason people sometimes select that, that you can keep your hair. Some maybe 60% of women kept 50% or more of their hair. With the TAC or ACT, it’s lower because the AC is so tough on the scalp, and it has been harder for people to coordinate that. But we have had patients use it with those regimens and had success.

So, I think in the end, really what we’re telling a patient is you have a tumor that looks scary on paper and on exam, but the chance you’re going to have an excellent response and be cured of your cancer with modest therapy is very, very good.

Transcript edited for clarity.

• A 53-year-old woman was referred to a breast surgeon after finding a mass in her left breast
  • PMH: unremarkable
  • FH: no history of cancer in first-degree relatives
  • PE: revealed a 6 X 5-cm, non-fixed mass in the left inferior breast without skin changes or nipple discharge, and palpable lymphadenopathy in the left axilla
  • ROS: clear
• Mammogram confirmed a left-sided, poorly defined spiculated mass. Ultrasound shows a 5.3-cm solid mass and enlargement of 2 left axillary nodes with thickened cortex
• Pathology results:
  • Core needle biopsy from the breast mass confirmed grade 3 invasive ductal carcinoma
    • ER—,PR—,HER2IHC 3+
    • FISH,HER2copy number, 15;HER2:CEP17 ratio, 7
  • Fine-needle aspiration of one left axillary lymph nodes was positive for carcinoma
• Staging: T2bN1M0