Adjuvant Therapy in HER2+ Breast Cancer

Ruth O’Regan, MD:The idea of a multidisciplinary approach to breast cancer really is gaining more and more momentum. What it basically means is that the patient, when they come into the clinic, sees not just a surgeon—which is the usual route that they go—but they also see medical oncology and then also radiation oncology. For patients withHER2-positive breast cancer, it really is very important to take a multidisciplinary approach because very often we will recommend preoperative chemotherapy andHER2-directed therapy, which offers the patient the advantage of downstaging the cancer so that she may end up needing less surgery to the breast. But it also allows us to get a better idea of what her prognosis is going to be based on the response to the preoperative treatment. So, in the patient whom we just referred to, it certainly would be possible—given the characteristics of her cancer and that it was estrogen receptor-negative andHER2-positive—that her cancer could have been markedly downstaged by the use of chemotherapy andHER2-directed therapy in the preoperative setting. And I think that would have given us a better idea of her prognosis as well.

I think it’s hard to estimate for sure what this lady’s risk of recurrence is because even though she has an advanced-stage cancer—in that it’s T2N3 and she has a lot of lymph nodes positive—we know from the adjuvant trastuzumab trials that we can still cure those patients with the use of adjuvant trastuzumab and chemotherapy. If she had been treated preoperatively, we could have had a better idea of her prognosis based on her response to preoperative chemotherapy andHER2-directed therapy. If you look at the old literature, certainly she would have a very high recurrence rate if she did not receive systemic therapy andHER2-directed therapy. But really, if you look at the data that are out there, many of these patients, the majority of them, are actually cured even with this later stage cancer.

The rationale for adjuvant therapy is the idea of killing micrometastatic cancer cells that have spread away from the primary cancer and are somewhere in the bloodstream, somewhere in the body essentially. Now, we can’t detect them, so we can’t know for sure that they’re there, but we do know that if you use systemic approaches—in this case with chemotherapy andHER2-directed therapy—you can kill these micrometastatic cells and basically prevent the cancer of recurring and hopefully cure the patient. So, that’s the rationale for adjuvant therapy. One of the problems is you don’t have anything to follow, so we’re really using large randomized trials—where we know the patients who got the chemotherapy andHER2-directed therapy had a lower risk of recurrence than the patients who just got chemotherapy—to base our decision on. But overall, that’s the idea behind it: to kill micrometastatic cells.

There are a number of options for adjuvant therapy for this lady. Firstly, you could consider using an anthracycline/taxane-based regimen along withHER2-directed therapy. So, for example, adriamycin/Cytoxan followed by weekly paclitaxel/trastuzumab has been shown to be very effective in this setting in reducing the risk of recurrence. More recently, we now have data with pertuzumab added into this scenario. And because this patient has node-positive disease, it would be very reasonable to give her adriamycin/Cytoxan followed by weekly paclitaxel or 3-weekly docetaxel along with pertuzumab and trastuzumab. The downside of that approach is that when you give an anthracycline with trastuzumab and probably otherHER2-directed agents as well, you increase the risk of cardiomyopathy and issues with the heart. So, you have to very carefully monitor that. But most of the studies have shown that the rate of cardiomyopathy is actually reasonably low, and certainly the benefits for a patient like this would certainly outweigh the risks.

Another option for adjuvant therapy would be to use a non—anthracycline-based regimen, which most commonly is docetaxel/carboplatin/trastuzumab with or without pertuzumab. This is a regimen that has been used extensively, and the combination of docetaxel/carboplatin/trastuzumab has been shown to be similar in benefit to the adriamycin/Cytoxan followed by paclitaxel and trastuzumab. So, although those patients do numerically better with the anthracycline-containing regimen, there’s really no significant difference. And the advantage of this regimen, the docetaxel/carboplatin/trastuzumab and pertuzumab, is that the risk to the heart is much lower. And if you do see any decrease in ejection fraction, they tend to be reversible versus when you give an anthracycline when they’re commonly not reversible. So, personally for this lady, I would probably consider docetaxel/carboplatin/trastuzumab, but I would also consider pertuzumab because of the node-positive status of her cancer.

Transcript edited for clarity.

• A 49-year-old women was referred for biopsy after routine mammography showed a 2.4-cm diameter spiculated mass in the left breast
• PE: revealed a well-circumscribed, non-tender firm mass in the lower-outer quadrant of the left breast; singular palpable nodal enlargement in the left axilla
• Excisional biopsy of the breast and axillary lymph nodes showed high grade lobular carcinoma
  • ER-/PR-; HER2 IHC 3+; Ki-67, 89%
  • Staging, pT2N3M0
• She underwent right mastectomy and lymph node dissection
• The patient was started on adjuvant chemotherapy with docetaxel + carboplatin with 12 months of trastuzumab + pertuzumab