You are here: Home: Meet The Professors Vol. 2 2004: Case 6
- Presents with a large central mass in her right breast with an inverted nipple and bulky nodes
- Experiencing generalized pain from diffuse bony metastases requiring narcotics
- Elevated CA27-29
- Biopsy revealed an ER/PR-positive, HER2-negative infiltrating ductal carcinoma
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| Key discussion points: |
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Management of the premenopausal patient with ER-positive metastatic disease |
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Ovarian suppression plus hormonal therapy for metastatic disease |
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Mastectomy and breast reconstruction for the young patient with metastatic disease |
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DR BAJAJ: This patient was a relatively healthy 39-year-old married computer technician with no children. When she presented she had a rather obvious large central mass occupying most of her right breast. Her nipple was inverted, and there were also bulky nodes in the axilla. She having generalized pain, which she thought was musculoskeletal but turned out to be the result of diffuse bony metastases. Most of her bones were involved on the bone scan, and her alkaline phosphatase was about 800. Her CA27-29 was elevated and her performance status was one. There was no one site that hurt her the most, but she needed narcotics for pain control. Her biopsy revealed an infiltrating ductal carcinoma that was ER/PR-positive and HER2-negative.
DR FOX: This is a case for which I would not necessarily rely on hormonal therapy as my first intervention, simply because it could take several weeks for her to respond to hormonal therapy. With a patient who requires a narcotic for pain, leapfrogging right to systemic chemotherapy with a doxorubicin-based regimen for a short time might be the responsible thing to do.
Response rates among different anthracycline-based regimens as first-line therapy don't differ much. If our objective is to give her the greatest degree of pain relief, we should probably seek something that has a legitimately high risk of response, such as doxorubicin/cyclophosphamide or doxorubicin/docetaxel. This would not be a long-term plan. It would be enough to make her feel better and then switch to some form of hormonal intervention, which in this case should probably be ovarian ablation.
DR ELLEDGE: She has a large amount of bulky disease, which influences my decision. I'd recommend hormonal therapy up front in this case. Because the tumor was strongly ER and PR positive, she has a high likelihood of response. Our neoadjuvant studies with aromatase inhibitors have a response rate of 60 percent. If she didn't have bulky disease, I would consider an LHRH agonist and tamoxifen as initial therapy. If she had a really large tumor, I might consider chemotherapy. With this type of case, being at the bedside would help my decision.
DR LOVE: Let's hear more about the bedside. What went on in your discussions with her, and what did you decide to do?
DR BAJAJ: I staged her and looked for metastatic disease, and there were no other sites of metastases. She had locally-advanced breast cancer and diffuse bony metastases, which were controlled with an analgesic. At that point I decided to start her on tamoxifen for about two to three months; then I added goserelin. She was slowly getting better. Her breast mass slowly decreased, her pain was controlled and her tumor markers started to come down after about three months, so we continued this combination.
She basically had a continued slow response over six months with this combination treatment. I was able to get her off the narcotics completely, and she remained narcotic-free for about 18 months after that.
In the meantime, I was concerned about her locally advanced disease, so about nine months into treatment, when she was in remission, I sent her for a toilet mastectomy. There was a significant amount of tumor in the central part of her breast, with multiple positive nodes. The margins came back negative and she chose to have immediate reconstructive surgery. In fact, she had her other breast enlarged at the same time. That's what she wanted, so I did not object to it. After surgery she underwent radiation to the chest wall.
DR LOVE: What was the cosmetic outcome, and how was her quality of life at that point?
DR BAJAJ: It was fine. There was no complication. She was working full-time, off narcotics and fully functional. Her tumor markers came down quite a bit but never really normalized. Slowly, over the past six months, they have started to go back up. She was asymptomatic and started to have pain again. This past December we switched her to anastrozole because she was having more pain and rising tumor markers. I continued the goserelin and zoledronic acid.
DR ELLEDGE: That is exactly what I would have done. I would have performed a toilet mastectomy on this patient for a couple of reasons. This woman has basically neglected an ER-positive breast cancer that she could live with for many years. She has no visceral metastases and has bulky disease. If it got out of control, radiation therapy would not handle it, so I would have done exactly the same thing.
In terms of reconstruction, I have had one patient, a very young woman in her twenties with metastatic disease, who strongly wanted reconstruction. Her disease was controlled and she had an implant reconstruction. I went along with it but would not agree to a TRAM flap.
DR LOVE: Kevin, earlier you said you have not used ovarian suppression plus an aromatase inhibitor in the adjuvant setting. What about that same strategy in metastatic disease?
DR FOX: In this case, I think it makes the most sense as a backup plan in case the combination of the LHRH agonist and tamoxifen fails. We have done that plenty of times, mostly in patients who are already ovarian ablated or suppressed in whom the change to an aromatase inhibitor is just natural.
DR FAVIS: I'm a little perplexed. If you're going to give her an LHRH agonist and make her postmenopausal anyway, why give her tamoxifen when you know that an aromatase inhibitor is actually a better drug?
DR FOX: That's a very good question. Without meaning to be cynical, the choice of first-line therapy is not terribly important as long as we feel she is going to respond to it. There is probably an additive response by giving ovarian suppression and tamoxifen or an aromatase inhibitor over ovarian suppression alone. However, it is really the sequence of therapies that is going to matter in the end. I would take it one step further and say it would also be justifiable to give her ovarian suppression by itself.
DR LOVE: Richard, what would you do if this woman has a good response to the anastrozole and LHRH agonist and then progresses? Again, she has no life-threatening disease.
DR ELLEDGE: I would consider fulvestrant or a different class of aromatase inhibitor. Lacking any objective data, I'd probably continue the LHRH agonist.
DR FOX: Most of what we know about these compounds comes from their use in endometriosis. Young women have a remarkable ability to resume normal menstrual function even after receiving this agent for a year or two, so I would agree to continue administering it.
DR ELLEDGE: In order to provide some controversy, if she responded and failed a different aromatase inhibitor or fulvestrant, I might come back with five days of DES three times a day. I think that using high-dose estrogens to change the estrogen environment as much as possible is quite toxic to breast cancer cells.
DR LOVE: Kevin, have you done that recently?
DR FOX: No, but I like the idea.
DR LOVE: In a premenopausal woman?
DR ELLEDGE: I wouldn't do that in a premenopausal woman, but this patient has been postmenopausal for a couple years.
DR LOVE: You said you'd stop the LHRH agonist?
DR ELLEDGE: Yes, I would stop the LHRH agonist when I went from below postmenopausal levels of estrogen to high-dose estrogen. Giving high-dose estrogen to premenopausal women is ineffective.
DR ABEL: Can you obtain DES these days?
DR ELLEDGE: You can, but it has to be compounded. For a while, I used PremarinR, but was very uncomfortable with that because I really did not know the dose. Most large cities have a compounding pharmacy that can compound it at five milligrams TID. I see a couple of patients a year who come to me for second opinions after having three, four or five hormones. I put them on DES, they respond and feel good, and I look like a genius.
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