Consideration for Neoadjuvant Treatment in HER2+ Invasive Ductal Carcinoma

Ruth O’Regan, MD:This is a 33-year-old premenopausal lady who felt a mass in her right breast. Importantly, her sister had unfortunately died from breast cancer at the age of 43, so she immediately went for further imaging and was known to have about a 3-cm speculative mass on mammogram that was confirmed by ultrasound. The ultrasound also showed a prominent lymph node in the right axilla. So, she went ahead and had a biopsy of the breast mass, and also an aspirate done of the lymph node. The breast biopsy showed invasive ductal cancer, ER-negative/PR-negative/HER2-positive. And the aspirate of the lymph node was also positive for metastatic cancer. At this point, I think this patient is an ideal candidate for a preoperative approach. We know that she’s going to require systemic therapy with chemotherapy and HER2-directed therapy because she has a positive lymph node. The cancer looks like it’s about 3 cm, so it makes perfect sense for her to have a preoperative approach, which offers the possibility of downstaging the cancer and also determining how responsive the cancer is to the treatment.

As far as a patient like this is referred for preoperative treatment, first of all, I think most of us would consider a preoperative approach in this patient. You could do surgery and treat her on the back end with HER2-directed therapy and chemotherapy, but I think in a patient like this, particularly with the positive lymph node, most of us would feel more comfortable using a preoperative approach. And what we would do is give a combination of chemotherapy with HER2-directed therapy. In the preoperative setting, we always use the combination of both trastuzumab and pertuzumab. And, as far as the chemotherapy, you could either do it with a taxane followed by an anthracycline-based regimen, an anthracycline-based regimen followed by a taxane plus trastuzumab/pertuzumab, or you could use a non-anthracycline-containing approach with docetaxel/carboplatin/trastuzumab/pertuzumab. Either of those would be very reasonable in a patient like this. The things we would think about are fertility issues. We have more data with using an anthracycline and a taxane in terms of maintaining fertility for a patient like this versus using the docetaxel/carboplatin regimen. So, I would probably take that into account.

And then, I take into account other preferences in terms of toxicity of the agents. If you actually look at the comparison of non-anthracycline versus anthracycline-containing HER2, HER2-directed therapy regimens in the adjuvant setting, the non-anthracycline and anthracycline are pretty much equivalent. So, they probably are in this setting, as well.

I think for a patient like this—being discussed or seen in a multidisciplinary clinic with a breast surgeon, medical oncologist—in most cases, the consensus would be to use a preoperative approach in order to downstage the cancer and see how responsive it is to systemic therapy.

As far as the goals of neoadjuvant therapy, there are a number of them. There are pros and cons, of course, with everything. One of the main reasons we use a preoperative approach is to try and downstage the cancer. So, if you have somebody that comes in needing a mastectomy, we know that by using preoperative systemic therapy, you can downstage them, allowing breast conserving surgery, for example. Sometimes you have no choice. If the patients have locally advanced breast cancer, they can’t do surgery at that time point. Then, certainly preoperative treatment is most certainly the best approach for a patient like that.

So, I think downstaging the cancer is historically the main reason that we’ve given a preoperative systemic therapy. However, more and more I think the general consensus is if the patient needs systemic therapy with chemotherapy and HER2-directed therapy, it makes more sense to give it before surgery versus after surgery. Because, you can see if the cancer is responding versus if you give it after surgery, you really don’t know if the cancer is responding, what you’re treating basically.

One of the key things about this, particularly in a scenario like this where you have a HER2-positive, hormone receptor—negative cancer, is that there is a reasonably high rate who achieve a pathologic complete response. And, if you achieve a pathologic complete response in a patient like this, their prognosis has been shown to be extremely favorable. It also gives you prognostic information for a patient. The downsides that some people will report are you never really know the exact stage of the cancer because if it responds to the chemotherapy and the HER2-directed therapy, you may never know how many lymph nodes were positive, for example. But, I think more and more, that kind of information isn’t really directing what we’re doing in terms of treatment. So, that’s why I think most of us are very comfortable using a preoperative approach for a patient like this.

Case Scenario 2:

• This is a 33-year old pre-menopausal woman who, after palpating a mass in her left breast, was referred for a mammogram by her primary care physician. Family history includes a sister who died of breast cancer at age 43 years.

• Her mammogram revealed a spiculated mass in the upper outer quadrant of the left breast. Targeted ultrasound showed a 2.6 x 3.4 x 2.1 cm irregular mass with an indistinct margin. Prominent appearing right axillary lymph nodes.
• Pathology: core biopsy revealed an invasive ductal carcinoma, poorly differentiated, lymphovascular invasion present. The tumor sample was mammaglobin-positive, ER/PR-negative, and HER2 3+ by IHC. Axillary ultrasound with fine-needle aspiration which was also positive for nodal involvement.
• The case was presented at the breast cancer multidisciplinary tumor board. The team recommended neoadjuvant therapy before surgery.