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Select Excerpts from the Interview
Tracks 1-5
DR GEYER: Initially, I told this patient that the available data suggested that
for patients with node-negative, ER-positive disease, the absolute improvement
with adjuvant chemotherapy was about four percent for disease-free
survival and a little less than that for overall survival, based on her profile. I
entered this patient’s information in Adjuvant! Online and showed her those
numbers. Her attitude was, “It’s got to be better than that for me to receive chemotherapy.” We discussed the Oncotype DX assay and that the patients
with a high recurrence score derive substantially larger benefits from chemotherapy
— a 28 percent absolute increase in freedom from distant recurrence
(Paik 2006; [5.1]).
She agreed that if that information were available, then she would reluctantly go ahead with chemotherapy. I believe that’s an important element — you do need to decide before you order the test whether the results will alter how you manage the illness. Her Oncotype DX results came back with an intermediate score of about 20. For her, that said no to chemotherapy.
DR LOVE: Hope, in your experience, when you see younger women like this
with an intermediate recurrence score of 20, how do they feel about chemotherapy?
DR RUGO: I believe it’s 50-50. It depends on the patients themselves. If
they’re absolutely sure they won’t want to receive chemotherapy, you might
choose hormone therapy before conducting the assay. Because those patients
are randomly assigned to hormonal therapy with or without chemotherapy in
TAILORx (Figure 2.1, page 8), either approach is currently acceptable.
DR LOVE: It’s interesting, Chuck, that before the Oncotype DX assay, most
patients with 1-cm, ER-positive tumors were receiving chemotherapy.
DR GEYER: Yes, it was usually recommended.
DR LOVE: Hope, a study conducted in a community practice setting in Colorado
showed that about one out of four times the Oncotype DX assay was ordered, it
changed what the oncologist did (Oratz 2005). What’s your experience with it?
DR RUGO: It’s interesting that the Colorado survey, which assessed the use of
the test when it was quite new, showed that result. It’s probably more like 50
percent now. I find that the test is even more useful for women who have Grade
II, Stage IC tumors, for which we would have reflexively used chemotherapy.
Now I avoid administering it to approximately 50 percent of those women.
DR HYAMS: I believe it’s worthwhile for surgeons to consider using tests
like Oncotype DX to help prepare the patient and explain her risk. If we’re
concerned about the overuse of cytotoxic therapy, it helps for the patient to be
brought into that loop a little sooner.
DR LOVE: We also want to talk about the issue of hormonal therapy for this
patient. She was 49 years old and postmenopausal according to her estradiol
and FSH levels, and she had stopped having her menstrual periods 18 months
previously. How do you approach deciding whether a woman is postmenopausal
or premenopausal when you factor in age and time since her last period?
DR GEYER: In a case like this, we know that aromatase inhibitors can
reinduce ovarian function in some women. In this case, being amenorrheic for
18 months and having postmenopausal estradiol and FSH levels, it’s likely that
she is permanently postmenopausal.
Generally with these women, I transition through tamoxifen for a year or two, so I don’t encounter reinduction of ovarian function. I don’t believe the data indicating the aromatase inhibitors are superior to tamoxifen are so compelling that one needs to be concerned about that, particularly if you’re forgoing chemotherapy because the patient has less aggressive disease and a better prognosis.
However, this patient had a history of a hypercoagulable syndrome associated with stroke. She didn’t want to go near tamoxifen, so we’re starting her on an aromatase inhibitor. I will watch her estradiol and FSH levels more closely than normal to see if her ovarian function starts to come back.
Tracks 6-9
DR HYAMS: This patient was ambivalent about chemotherapy, and she was
highly motivated to maintain her lifestyle. By the same token, she didn’t want
to give up an opportunity for cure. She recognized that a breast cancer recurrence
would be associated with ultimate mortality, likely from breast cancer.
When we received this patient’s information, it became reasonable to turn around and say, “We have a test that appears to work well. It’s been reasonably well validated, but there is an area in which some questions remain. Would you have an interest in participating in a study?
If you participate in TAILORx (2.1) and you’re in the low-risk category, you receive the hormonal therapy of your choice. If you are in the high-risk group, you receive hormonal therapy and chemotherapy. The intermediate-risk group is the group for whom we’re most interested in teasing out the advantages.”
She was willing to participate in the trial, and she received a recurrence score of 25, which put her on the top end of the intermediate-risk category. She was randomly assigned to receive hormonal and cytotoxic therapy.
DR RUGO: Many oncologists would not generally use chemotherapy for a
postmenopausal woman who has a 0.8-cm, ER-positive, PR-positive tumor.
Yet we may, in that situation, be undertreating the patient. So it’s important to
figure that out. I applaud you for enrolling this patient in the trial.
DR LOVE: How did this woman feel about being randomly assigned to
chemotherapy?
DR HYAMS: Because her recurrence score was essentially at the cutoff point
for intermediate- to high-risk disease, I believe it was an easier choice for her.
I have to say that even I’m uncomfortable randomly assigning a patient with a
recurrence score of 12, which would be low risk, but we all agreed when we
were planning this trial to be extremely conservative. That’s why those cutoff
points were chosen.
Tracks 11-13
DR RUGO: This patient presented a little less than a year before the first data
with adjuvant trastuzumab were reported (Piccart-Gebhart 2005; Romond
2005). As we approached the reporting of the data from those trials and we
couldn’t accrue patients to the trials any longer, many of my colleagues and I
considered the use of adjuvant trastuzumab outside of a clinical trial.
This woman presented with a large tumor and a palpable node. She was young with a nasty tumor, and I felt she deserved trastuzumab as part of her therapy. So she received an anthracycline for four cycles followed by a taxane- and trastuzumab-based regimen.
She had moderate, continued shrinkage of her tumor throughout the AC and the trastuzumab/ paclitaxel. The node quickly became nonpalpable. Then she underwent a skin-sparing mastectomy and reconstruction. At the time of her surgery, she had a small amount of invasive cancer and a small amount of disease in one node.
She received radiation therapy after her surgery and did well. Then we had a discussion about her hormonal therapy options. As she had residual disease at the time of her surgery and was young with an aggressive presentation, I believed she still had substantial residual risk of recurrence and death from breast cancer.
So we thought she would potentially benefit from ovarian suppression. A lot of the data with subsets have suggested that women under age 35 might not benefit as much from hormonal therapy with tamoxifen, potentially because they have high levels of circulating estrogen. So we recommended ovarian suppression, and she is continuing to receive monthly leuprolide.
She started initially on tamoxifen, but she did not tolerate it. She experienced severe and unremitting hot flashes, despite medical therapy, and morning nausea, which is seen in approximately five percent of women receiving tamoxifen. So we switched her to anastrozole, which she tolerates well. She has a little joint stiffness, minimal hot flashes and some vaginal dryness. She is otherwise doing well approximately 3.5 years after the initial diagnosis.
We have been hesitant to use the aromatase inhibitors in very young women, even those on GnRH agonists, because you can potentiate ovarian function. Women may recover their menses, but this woman continues to show good ovarian suppression.
| Table of Contents | Top of Page |
Editor:
Neil Love, MD
Interviews
Melvin J Silverstein, MD
- Select publications
David M Hyams, MD
- Select publications
Charles E Geyer Jr, MD
- Select publications
Hope S Rugo, MD
- Select publications
Highlights of a CME Symposium Held in Conjunction
with The American Society of Breast Surgeons Eighth
Annual Meeting
- Select publications
A CME Audio Series and Activity
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