•	A mother in her early 30s with two young children
•	1.7-cm infiltrating ductal carcinoma (ER-negative, PR-negative, HER2-positive [FISH])
•	Lumpectomy and AND (7/9 positive nodes) and radiation therapy
•	Received AC x 4, paclitaxel x 4
•	Became pregnant 4 months post-treatment
•	Developed right arm/shoulder pain and numbness in hand 1 month later
•	Exam: Supraclavicular fullness
•	MRI: 4 x 4 cm right supraclavicular mass involving the brachial plexus
•	FNA and open biopsy: Negative for tumor
•	Pain increased, developed shortness of breath
•	At 25 weeks gestation, right pleural effusion was discovered; fluid was positive for adenocarcinoma

Key discussion points:
	Defining the goals of therapy for a pregnant patient with metastatic disease
	Risks and benefits of systemic therapy for metastatic disease in pregnancy
	Effects of pregnancy on breast cancer progression
	Emotional impact of practice on the oncologist

Dr Love: Dr Harth, would you describe your discussions with this woman and her family in terms of their expectations and goals for therapy and for the future?

Dr Harth: The extent of the disease was not determined until she was at 25 weeks gestation, and she wanted to be aggressive with therapy and try to live as long as possible. Her family was very dependent on her. The main question was: What therapies could we offer?

Dr Love: How did you discuss the potential effects of therapy on the fetus?

Dr Harth: I told her we were unsure of the impact many chemotherapy agents could have on the fetus. In addition, we discussed the fact that we didn’t know whether she would respond to treatment. She had a very aggressive tumor, which relapsed within a short period of time after adjuvant therapy.

Dr Love: Dr Seidman, how would you think through this case?

Dr Seidman: Thank God we don’t see this situation very often. This is an incredibly difficult case in which we’re actually considering the fates of two lives — one confronted with metastatic breast cancer and another that hasn’t yet begun.

This woman needs to understand that treatment is unlikely to have any curative potential. Hopefully, this will factor into her decision regarding the potential toxicities of therapy to which her fetus would be exposed. Some of these concerns are probably not as great as we might imagine, because she is well into her second trimester; therefore, most organ system formation has already occurred.

I would consider trastuzumab, because this agent doesn’t have the classic toxicities of chemotherapy, but I do not know whether trastuzumab crosses the placenta nor do I know its potential toxicity to the fetus.

This patient’s disease is rapidly progressing, causing brachial plexopathy, a malignant pleural effusion, and she still has to go through childbirth. I would want to medically maximize her chances of a good outcome in delivering this child. It will take eight to twelve weeks before this woman reaches steady state concentrations of trastuzumab; therefore, in addition to trastuzumab, I would likely add a cytotoxic agent. My bias would be to use carboplatin, vinorelbine, or gemcitabine in combination with trastuzumab because she recently received an anthracycline and a taxane.

Dr Tripathy: I would try very hard to hold off on any therapy until she delivers. Apart from the pleural effusion, which can be tapped for symptomatic relief, I don’t think there is a pressing, life-threatening reason to treat her. I think she should wait until delivery, which is 10 weeks away, at most.

We have ample evidence that antibodies do cross the placental barrier, and I would suspect that trastuzumab crosses through the placenta. The HER2 pathway is important in cardiac and neural development, and I am concerned about using trastuzumab in pregnancy at any stage of fetal development. I am postulating all of this, but I don’t think we can exclude harm.

I would let her deliver and then institute palliative chemotherapy. At that point, your choices are much greater, and I would certainly use trastuzumab-based therapy.

Dr Love: Debu, what would it take for you to give her chemotherapy? For example, how would you deal with the situation if two weeks later her pleural effusion was becoming worse, she had mediastinal lymph nodes, and her pain was increasing?

Dr Tripathy: I would probably use induction chemotherapy with an anthracycline and cyclophosphamide. These chemotherapy agents are not optimal because she has already received them, but there is data from MD Anderson looking at this combination as adjuvant or neoadjuvant therapy. Fluoropyrimidines, such as capecitabine, would also be a reasonable choice if we are up against the wall. As soon as she delivers, I would add trastuzumab and revert to a combination like vinorelbine/trastuzumab in a patient like this who has received a taxane.

Dr Love: Andy, a related issue in this case is advising premenopausal women about becoming pregnant after having breast cancer. How do you approach this?

Dr Seidman: Because this woman’s risk of relapse was high, particularly in the short term, and because she was in her early 30s, I would have urged her to wait before conceiving. This is always a long and careful discussion, but for a younger woman, I would strongly urge the “watch-and-wait” approach. I don’t tell these women they can never become pregnant. We do not have good evidence that pregnancy increases the risk of relapse.

Dr Love: Would you have advised her against pregnancy if she had a lower risk of relapse, for example, if she had a smaller tumor with negative nodes?

Dr Seidman: Because of her young age, I still would have taken a “watch-and-wait” approach. Her fertility in her late 30s would still probably be quite acceptable, and I would like for there to be some “water under the bridge” so to speak.

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