Second Opinion

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its most active and plentiful metabolite. Antidepressants can inhibit CYP2D6 invarying degrees, so I like to hear that these patients have vasomotor symptoms.In terms of the arthralgias, I believe we need more insight into some of thepolymorphisms of the aromatase enzyme. It’s highly polymorphic, and I need tosee a paper showing a correlation between the arthralgias, polymorphisms andestradiol levels. I believe we will see that.DR LOVE: Does that mean you prefer to keep a symptomatic patient on anaromatase inhibitor if the side effects are tolerable?DR O’SHAUGHNESSY: Yes. Now, having read this paper, I would prefer formy patients to have some side effects. I worry a little about the asymptomaticpatients. However, most women will tell you that they’re at least stiff when theyget up to walk. I would estimate that two thirds of the women receiving anaromatase inhibitor experience musculoskeletal symptoms.3.2ATAC Trial: Annual Breast Cancer Recurrence Rate According toEndocrine Symptoms Reported at Three-Month Follow-UpAnastrozole Tamoxifen Overall Hazard ratio*(n = 1,967) (n = 1,997) (n = 3,964) (95% CI) p-valueVasomotorsymptoms 1.7% 2.4% 2.1% 0.84 (0.71-1.00) 0.04Joint symptoms 1.6% 1.9% 1.7% 0.60 (0.5-0.72)
From the practice of Isaac Levy, MDA 76-year-old woman underwent a modified mastectomy for a 6-cm, Grade III, ER/PR-positive, HER2-positive IDC. The tumor was staged as T4b with extensive dermalinvolvement. She received TCH, but during her sixth cycle she developed an intraabdominalabscess secondary to a perforated diverticulum, and treatment was stopped.She ultimately required a colon resection and then underwent closure of a divertingileostomy. She is now back to baseline but has been off therapy for six months.Track 57DR LOVE: Dr Levy questions whether to restart trastuzumab. Terry, whatdo we know about delayed trastuzumab?DR MAMOUNAS: We don’t have many data in this particular setting. We knowthat when chemotherapy is delayed, the benefit is decreased. I would havepreferred to restart trastuzumab once she recovered from the perforated diverticulitis,maybe within a couple of months of her last dose.We’re in uncharted territory at this point, but I believe it is logical to administertrastuzumab. In the HERA trial, sequential trastuzumab administered afterchemotherapy was still effective. I would administer trastuzumab to this patientfor at least another six months or so.DR SWAIN: I agree that we don’t have a lot of data, but we do know thattrastuzumab stays around a long time. The five half-lives from the five doses shedid receive gave her another several months of therapy. I also agree that I wouldhave administered the trastuzumab earlier, if the patient had agreed to it.Tracks 58-59DR LOVE: What about the idea of neoadjuvant trastuzumab for thispatient?DR SWAIN: I absolutely would have recommended it for this patient with a T4btumor and skin involvement. Aman Buzdar published data from a randomizedstudy for patients with operable, early HER2-positive breast cancer who receivedan epirubicin-based regimen with or without trastuzumab (Buzdar 2005).The patients who received trastuzumab had a pathologic complete response(pCR) rate of 65 percent, demonstrating a significant benefit with neoadjuvanttrastuzumab.At the 2008 San Antonio Breast Cancer Symposium, Dr Gianni presented anupdate of the NOAH trial, which randomly assigned more than 200 patientswith locally advanced, HER2-positive breast cancer to receive an anthracyclinebasedregimen with or without trastuzumab (Gianni 2008). The pCR rate was43 percent compared to 23 percent, respectively, so it was clearly beneficial toreceive trastuzumab (4.1).13
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