Breast Cancer Update Issue 1, 2008

DR CHARLES E GEYER JR: Our first choice for postmenopausal patients with hormone receptor-positive disease who have completed a standard five-year duration of hormonal therapy is to enroll them on the NSABP-B-42 study with a randomization to either letrozole or placebo. If this cannot be done, we try to attain a sense of the patients’ residual risk to decide whether to stop or continue therapy. We infer that based on their baseline risk from their disease at presentation — a larger tumor, a larger number of nodes and so on indicate a higher risk for recurrence. The assumption is that the relative reduction is fixed, so the residual risk beyond five years is higher.

If I have a patient with a large number of positive nodes, I discuss with that patient the uncertainties regarding benefits of additional therapy, toxicities and so on. I believe that you also have to assess how the patient tolerates the aromatase inhibitor.

Breast Cancer Update Issue 2, 2008

DR KATHY D MILLER: I tell patients that I have no clue if aromatase inhibitors should be continued beyond five years. We have available the rerandomization of the MA17 trial that evaluates 10 versus five years of an aromatase inhibitor in aggregate, and I’ve been talking to patients about the trial even though I must admit I’ve been surprised that I have not had a lot of patients who were interested.

I certainly could not argue with someone who had a patient at high risk who was tolerating the aromatase inhibitor well, who wanted to continue it and thought that was reasonable. But I believe that the patients in that situation need to know that we have absolutely no data to advise them as to whether that will provide a greater benefit, greater bone toxicity or if it will all be a wash in the end.

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Breast Cancer Update Think Tank Issue 1, 2008

DR JULIE R GRALOW: It’s not unusual to evaluate premenopausal patients with positive nodes and ER-positive, HER2-negative disease who request “anything to try to reduce the risk of relapse.” Younger patients have a chance of regaining ovarian function. If the patient is close to menopause, I have less of an issue with ovarian suppression because I think she’ll go through menopause regardless.

If she has chemotherapy and goes into a temporary menopause, I would want to enroll her in a trial. I don’t know what’s correct and incorrect with long-term follow-up. Hopefully, she will survive and will reach age 70 and beyond. The higher the number of nodes, the more comfortable I am with ovarian suppression and an aromatase inhibitor. That said, I would consider enrolling a patient like her in a trial such as SOFT. I would not say, “I am sure you shouldn’t have your ovaries suppressed.” I don’t know.

Breast Cancer Update Think Tank Issue 1, 2008

DR JOHN MACKEY: If a premenopausal woman came to me with ER-positive, HER2-negative disease and five positive nodes I don’t think ovarian function suppression with an aromatase inhibitor is appropriate — the evidence doesn’t exist. We know that if you use goserelin or other analogs, some patients actually have substantial levels of estradiol. In fact, we have anecdotes of women with metastatic disease who undergo ovarian function suppression and continue to menstruate. You can’t trust an ovary not to wake up again simply because someone’s received chemotherapy and has a temporary loss of menses.

At the end of the day, if a premenopausal patient was insistent on such an approach, I’d say that she might consider a laparoscopic oophorectomy, particularly if she has a family history by which you could bolster that argument. However, generally speaking I would suggest five years of tamoxifen as the standard and would say that clinical trials are attempting to address this issue, but the data are not at all definitive.

Breast Cancer Update Issue 3, 2008

DR FORBES: We learned some important concepts with this new 100-month follow-up data from the ATAC trial. First, the advantage of anastrozole over tamoxifen is maintained at least through nine years. Is has a carryover effect — the benefit continues after the treatment is stopped. In particular for the post-treatment period from years five to nine, the advantage of anastrozole compared to tamoxifen remains significant. Furthermore, the absolute difference in the rate of breast cancer relapse increases in magnitude from 2.8 percent at five years to 4.8 percent at nine years.

A somewhat unexpected and especially pleasing finding was that upon completion of the treatment, no difference was apparent in the risk of fracture between tamoxifen and anastrozole. The other surprising finding was the much lower rate of endometrial cancer in women receiving anastrozole compared to those on tamoxifen.

Breast Cancer Update for Surgeons Issue 1, 2008

DR ROBERT W CARLSON: The 100-month follow-up of the ATAC trial was one of the most important abstracts presented at San Antonio. The results were encouraging and reassuring. From the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) analysis, we know that the benefits of tamoxifen, in terms of risk reduction for recurrence and death, persist well beyond the period of actual tamoxifen administration. Some were concerned that this might not be the case with the aromatase inhibitors — that you might win the short game but lose the long game.

The efficacy data from the ATAC trial suggest substantial benefit from anastrozole beyond the five years of actual therapy. The long-term differences were larger in the ATAC trial than in the EBCTCG analysis of the tamoxifen carryover effect. It is an indirect comparison, so we have to be cautious, but it is reassuring to observe sustained benefits from anastrozole after treatment is completed.

Breast Cancer Update for Surgeons Issue 1, 2008

DR MONICA MORROW: Clearly, the results from the ATAC trial are holding up long term. A question was whether there would be a “carryover” effect with the aromatase inhibitors, as we’ve seen with tamoxifen, in terms of the long-term reduction in contralateral breast cancer and survival benefits. The 100-month ATAC trial data suggest that the same carryover effect is present, which is reassuring.

The idea that the osteoporosis and fracture problems appear to stabilize over time is also reassuring, although it doesn’t obviate the increased risk of osteoporosis in the early treatment period. This needs to be monitored and is an issue in the chemoprevention setting. Most of the side-effect profile of the aromatase inhibitors appears to be preferable to that of tamoxifen, with the exception of the bone and joint problems, which for some women can be significantly disabling.

Breast Cancer Update Issue 2, 2008

SIR RICHARD PETO: The ATLAS study compares 10 years of tamoxifen to five years in terms of the 15-year outcome. It involves a large international group with about 400 centers in 38 countries and is run by Christina Davies. They’ve randomly assigned 11,500 women who have completed five years of adjuvant tamoxifen. About half of the women had ER-positive disease, and half didn’t have their ER status tested, but most of them would have been ER-positive.

Christina followed the patients for an average of four years, so these are preliminary results. But it’s clear that further reduction in recurrence is achieved by continuing tamoxifen beyond five years. It decreases it further by about 15 percent. This decrease is in addition to the decrease from the carryover effect of the first five years. In terms of preventing recurrence, 10 years of adjuvant tamoxifen is better than five years. It’s too early to determine how 10 years of tamoxifen will affect breast cancer mortality. Also, longer treatment will increase the incidence of the significant side effect of uterine cancer. There are disadvantages in continuing tamoxifen, but certainly the myth that tamoxifen beyond five years will start stimulating breast cancer is wrong. This was a mistake that emerged in the mid-90s.

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Interview, April 2008

DR HYMAN B MUSS: Like the majority of survey responders, typically I don’t use further systemic therapy for a patient with residual triple-negative disease after neoadjuvant therapy. Generally, if a patient has a tumor that can be managed with breast conservation, I don’t treat her with neoadjuvant therapy. Rather, it’s for the patients with large tumors that I employ neoadjuvant therapy, and these patients usually agree to no further treatment because they are often reassured when they feel their tumor shrink from therapy prior to surgery.

A number of papers are being published evaluating response to neoadjuvant therapy and the risk of recurrence in patients with triple-negative breast cancer. Anderson and colleagues, in the Journal of Clinical Oncology, found that many of these patients fared well unless they had a large tumor and little response to treatment, which we would all agree is a bad scenario. However, I don’t believe we have a good enough database to accurately inform patients of their likelihood of relapse in this situation.

Breast Cancer Update Issue 6, 2007

DR O’SHAUGHNESSY: For a patient with significant residual triple-negative disease at surgery after neoadjuvant chemotherapy, I order a PET scan up front. It is particularly useful in highly proliferative tumors with a lot of axillary adenopathy, where we sometimes observe lymphadenopathy in the intramammary chain, in the low cervical nodes and even in the mediastinum. If the disease is chemotherapy sensitive and you have a chance for a decent prognosis, then you can include those nodal beds in the radiation port.

Off protocol, I generally recommend noncross-resistant chemotherapy agents in cases like this. In the absence of other data, I turn to agents with either a proven track record in the adjuvant setting or for which we have evidence of some preoperative activity.

I would probably choose capecitabine combined with a platinum agent and bevacizumab. Capecitabine is a noncross-resistant drug, and work from Farber and others suggests that it has some activity in triple-negative disease. I would try to give the patient the best chance for cytoreduction and disruption of any micrometastatic niche she might have.

Breast Cancer Update Issue 5, 2007

DR SHARON GIORDANO: Increasingly, data suggest that patients with ER-positive tumors benefit less from chemotherapy than patients with ER-negative tumors, but I’m not convinced at this point that they receive no benefit. Studies like TAILORx, in which we are stratifying patients with ER-positive disease by risk as determined with the Oncotype DX assay, might help establish whether there is a subset of patients who don’t need chemotherapy. For patients who are borderline candidates for chemotherapy, if they have ER-positive disease, I’m less inclined to use chemotherapy. I believe, however, that patients who have high-risk disease, even if it’s ER-positive, still clearly benefit.

In the TAILORx trial, which we are participating in, if a patient’s tumor is categorized as presenting intermediate risk, then she is randomly assigned to hormonal therapy with or without chemotherapy. If the patient’s tumor is in the low-risk category, she receives hormonal therapy alone. If the patient’s tumor is in the high-risk category, she receives chemotherapy and hormonal therapy.

I’ve used the Oncotype DX assay off protocol — to help both myself and the patient make a decision as to whether to use chemotherapy — for patients who are borderline candidates for chemotherapy because they do not want chemotherapy or they have comorbidities or fairly low-risk tumors.

I can’t say that I have a clear cutoff, but for patients with tumors larger than two centimeters, I’m inclined to use chemotherapy. I typically don’t order the Oncotype DX assay in that situation.

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Breast Cancer Update Think Tank Issue 1, 2008

DR NICHOLAS J ROBERT: I tend to order the test for patients with node-negative disease, with whom I would be comfortable administering endocrine therapy and there’s a question mark — such as a case in which the ER is not highly positive.

I’m a fan of Allred’s scoring, but frankly our pathologists don’t use it, so it’s not very helpful. In addition, I believe that the Oncotype DX test provides me with better insight in terms of the endocrine status of the tumor, because if the ER is low-positive and the PR is negative, if the recurrence score comes back as intermediate or high, that pushes the chemotherapy button for me.

Interview, May 2008

DR PETER M RAVDIN: The Oncotype DX assay truly has a role for smaller tumors, larger tumors and 2-to 3-cm tumors. However, the degree of accuracy changes. One of the limitations of Oncotype DX with regard to smaller tumors is that the assay was developed largely from the NSABP-B-14 and B-20 trials. These trials enrolled relatively few patients whose tumors were 10 millimeters or smaller in size. They were not excluded, but they made up a very small percentage of the patient population. Having said that, it can be argued that for the patients with smaller tumors, we are less confident that the Oncotype DX assay is valid.

I think the Oncotype DX assay is valid because a gene signature should help you tell the difference between low risk and high risk — in other words, high proliferation state or low proliferation state tumors. Additionally, I would expect this to apply to small node-negative tumors, larger node-negative tumors and node-positive tumors also. So far, the evidence seems to support this view.

One portion of the gene signature that needs to be better defined is whether other factors should be used in addition to the Oncotype DX assay. All things equal, a tumor with a given signature that had been around long enough to involve regional nodes will almost certainly have a worse prognosis. This is evidenced in the Southwestern Oncology Group 8814 trial.

Breast Cancer Update Issue 1, 2008

DR MACKEY: In deciding whether to use an anthracycline for patients with HER2-negative disease, my preference and what I discuss with patients is that we proceed with TC. I’m not administering anthracyclines to patients with HER2-negative disease unless the patient is adamant that she wants one of the older regimens. It’s clear that TC has achieved a survival advantage over AC, which is exciting because this population is unselected and includes patients with HER2-positive disease who did not receive trastuzumab. So in a sense this trial was stacked against the TC regimen, but TC is still outperforming AC in terms of safety and efficacy. With the survival advantage, I don’t see where the anthracyclines fit into the treatment of HER2-negative disease.

Breast Cancer Update Think Tank Live 2007

DR DENNIS J SLAMON: The US Oncology adjuvant trial evaluating patients with node-negative and node-positive disease demonstrated the superiority of the nonanthracycline-containing regimen over an anthracycline. At UCLA, most of the investigators and clinicians, including myself, are using docetaxel and cyclophosphamide (TC) instead of AC.

DR SANDRA M SWAIN: I feel comfortable not using an anthracycline for patients with node-negative disease. Perhaps it’s not rational, but I make a distinction for patients with higher-risk disease. Furthermore, Mike Press and Soon Paik have demonstrated that TOPO II isn’t overexpressed in patients with HER2-negative disease. Therefore, I don’t believe we need the anthracyclines for these patients.

DR MARK D PEGRAM: You must have a balanced discussion with the patient, and evaluate her comorbid medical conditions, et cetera. We have nice data comparing nonanthracycline regimens to anthracycline regimens, and clearly the nonanthracycline regimens are preferable. It boils down to a patient’s relative risk and which regimen she’s likely to tolerate. I use a lot of TC for patients with node-negative disease. Moreover, we participated in the Phase III trials of TAC versus FAC in the metastatic and adjuvant settings, so we have quite a lot of experience with docetaxel-based regimens at our institution. I feel comfortable using TC.

DR SLAMON: It’s clear that physicians are using TC now. The benefits are the same for patients with higher-risk disease as for those with node-negative disease. TC is easy to administer, and the patients finish their chemotherapy in 12 weeks.

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Breast Cancer Update Issue 2, 2008

DR KATHY S ALBAIN: I use the Oncotype DX assay when I am on the fence about chemotherapy, but I also order it when I think I know the answer. At ASCO 2007, we presented a multicenter study for women with node-negative disease of the impact of the Oncotype DX assay results on prospective decision-making by doctors and patients.

When you thought you knew what you were doing, you changed your mind in a third of the cases, either to use therapy when you hadn’t expected to or vice versa.

I’m not ready to say it will only be used when the patient and/or doctor are undecided about the use of chemotherapy, but those may be the types of patients with node-positive disease that we should start with. A woman with 15 positive nodes is not someone for whom I will order a recurrence score assay right off the bat.

Breast Cancer Update Issue 3, 2008

DR DANIEL F HAYES: Kathy Albain led a study (SWOG-8814) for postmenopausal patients with node-positive, ER-positive disease who were randomly assigned to tamoxifen alone, tamoxifen concurrent with CAF or CAF followed by tamoxifen. This trial demonstrated that chemotherapy concurrent with tamoxifen was not as effective as chemotherapy followed by tamoxifen. Tissue blocks were available from approximately 40 percent of those patients, so we evaluated whether or not we could correlate a benefit of treatment with the Oncotype DX recurrence score. We compared tamoxifen alone to CAF/tamoxifen. To our pleasure, we saw exactly what we predicted: Among the patients treated with tamoxifen alone, those with low recurrence scores as determined by Oncotype DX fared better than those with high recurrence scores.

However, nodes are still a prognostic factor. In fact, as many as 40 percent of patients with node-positive disease and low recurrence scores will experience a recurrence on tamoxifen alone. Among the patients with node-positive disease and high recurrence scores, a statistically significant benefit was seen in disease-free survival with CAF/tamoxifen versus tamoxifen alone. For the patients with low recurrence scores, the curves overlapped. Even in node-positive disease, chemotherapy may not be effective for patients with high ER, low HER2 or low Ki-67 — the components of the Oncotype DX assay.

For patients with node-positive disease, adjuvant chemotherapy is of proven benefit regardless of biological subsets. Almost every guideline recommends chemotherapy for patients with node-positive disease. The stakes are high in this situation. I don’t believe nodal status indicates whether chemotherapy will work — biology tells you whether chemotherapy will work. I am not sure whether this is the assay we should use to decide whether to withhold adjuvant chemotherapy from patients with node-positive disease.

The question is whether we should run yet another prospective randomized trial. It would be a large trial because it would be an equivalency trial. Patients with low recurrence scores who received adjuvant tamoxifen would be randomly assigned to modern chemotherapy versus none.

Breast Cancer Update Think Tank Issue 1, 2008

DR GRALOW: For a select group of patients with positive nodes, such as those with low nodal burden, I use the Oncotype DX assay to determine whether they should receive adjuvant chemotherapy. I am not ready to order it for a patient with 10 positive nodes and use it to trump the other features of her disease. For a patient who I believe is highly sensitive to endocrine therapy and has a little nodal disease, I would consider it.

DR CLIFFORD HUDIS: I recently saw a 78-year-old woman in otherwise good health with a 2-cm, ER-positive (100 percent), PR-negative (zero), HER2-normal tumor and a single positive lymph node out of 14. Her attitude was that she would accept chemotherapy if it was needed. That was one of the first times I’ve ordered an Oncotype DX assay for a patient with node-positive disease.

Conversely, I believe it is risky to withhold adjuvant chemotherapy from cohorts of patients for whom it’s been recommended, especially among those with node-positive disease, based on relatively small absolute numbers of events. When the patient is on the fence about receiving chemotherapy and you’re having a discussion, that’s a different situation.

DR MUSS: It is reasonable to use Oncotype DX for a patient with one positive node who is on the fence about whether or not to take chemotherapy. Like Cliff, I would be nervous about using this routinely, except for an occasional patient. Also, these studies we’re discussing have notably small numbers of patients. We’re pruning them down and ending up with 200 patients in a subset analysis. We need to be cautious.

Breast Cancer Update Issue 2, 2008

DR JOYCE O’SHAUGHNESSY: People aren’t wrong to use TC for higher-risk, node-positive disease, but the question of duration remains for patients with a higher nodal burden and presumably a higher micrometastatic burden. The question is whether four cycles are enough, so most of us will err on the side of six or eight.

I use TC all the time in cases for which I used to use AC, which were for the patients at lower risk, such as those with ER-positive, node-negative disease or the patients with tiny triple-negative disease, who will gain that one to four percent absolute benefit from chemotherapy.

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Breast Cancer Update Issue 2, 2008

SIR PETO: In 2007, we presented the updated meta-analysis of trial results at the San Antonio Breast Cancer Symposium. We don’t have trials of taxane-based regimens versus no adjuvant therapy, but we have trials of taxane-based regimens versus anthracycline-based regimens. These regimens will not be so different, but the taxanes are better.

From the data we have at the moment, taxane-based regimens appear to involve about a 15 percent lower recurrence rate and lower breast cancer mortality rate versus anthracycline-based regimens. With anthracycline-based regimens versus CMF, about a 15 percent lower recurrence rate is evident. I don’t mean a 15 percent absolute reduction: These are proportional risk reductions.

To evaluate chemotherapy, we have to put various trials together. CMF versus nothing provided a moderate gain. Anthracycline-based therapy versus CMF provided another moderate gain. Taxane-based regimens versus anthracycline-based regimens provided yet another moderate gain.

If you combine all of these, then you conclude that if we had been comparing taxane-based regimens to no adjuvant therapy, for women in their fifties and sixties we’d probably be reducing breast cancer mortality by about one third and recurrence rates by about half. For the younger women, the effects are even greater. Taxane-based regimens would be reducing breast cancer mortality by about half and recurrence rates by more than half.

Breast Cancer Update Issue 2, 2008

DR MILLER: When I see a patient with a HER2-negative tumor with multiple positive nodes, I generally administer AC/paclitaxel, evenly split between dose-dense administration and using the paclitaxel weekly.

Interview, April 2008

DR MUSS: If presented with a patient who has had prior breast cancer, was treated with an anthracycline and a taxane and now presents with triple-negative contralateral disease, I would probably use TC now. I’d be repeating one drug that she’s already had, but I don’t think that’s risky for leukemia, and perhaps there is synergy for TC, so that is what I would recommend.

Another option in this situation, although I haven’t seen this much, might be docetaxel/capecitabine. I’ve also seen vignettes of platinum data in this situation and the in vitro work of Lisa Carey, but I’m not sure that’s worked out so well. I’ve never been a great platinum fan, but it’s interesting to see.

Breast Cancer Update Issue 7, 2007

DR GOSS: Treatment of triple-negative breast cancer is a special interest of ours at MGH Cancer Center. Everyone recognizes that triple-negative disease is a disproportionately fatal form of breast cancer and that it’s particularly refractory to our current anticancer therapies, and we are frustrated by the lack of progress with this dangerous subtype. Cisplatin was previously tried in breast cancer and produced a low response rate in an “all-comers” setting, so it was taken off the table as a single agent or even as an active drug in breast cancer.

However, Leif Ellisen, the head of translational research at MGH Cancer Center, is investigating cell survival pathways in breast cancer, and he has discovered a p63/p73 marker that we believe identifies 30 to 40 percent of patients with triple-negative breast cancer who are exquisitely and specifically sensitive to cisplatin. These genes are in the same family and pathway as p53.

So it makes biological sense that a platinum agent would be particularly effective in this subgroup of patients. It is more than simply a predictor of response — it’s actually involved in the response mechanism.

In the clinical setting, I would not use single-agent cisplatin before standard chemotherapy, but I would afterward.

I’ve seen responses with the strategy, and I believe that this will be one of these phenomena in which the marker may be found in only 15 or 20 percent of patients. Among those patients, we’ll see an 80 or 85 percent response rate with this drug, which would be fantastic.

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Breast Cancer Update Issue 1, 2008

DR ROBERT: You have to be careful in how you approach adjuvant chemotherapy in patients with smaller HER2-positive, node-negative tumors. Age is key, as is making sure the tumor is truly HER2-positive. As a former pathologist, I like to see the grade to be at least II or III. However, I have a low threshold for intervening with a HER2-based regimen for tumors larger than five millimeters. For tumors smaller than five millimeters, the data are sparse. If it’s hormone receptor-negative, I struggle.

Breast Cancer Update Issue 2, 2008

DR NANCY U LIN: One area in which we need more data in terms of actual prognosis or natural history is for the patients with HER2-positive, T1N0 tumors. HER2 wasn’t routinely tested until about 1999 or 2000, after trastuzumab was approved, so it’s difficult to obtain, for example, 10-year follow-up data on a large cohort of patients. I believe that’s part of what has limited our ability to answer this question.

At any given tumor board, the recommendations range from four cycles of AC to AC followed by trastuzumab, similar to the HERA regimen. Most of us would not treat someone with a low resurgent positive tumor with the full North American regimen of AC/paclitaxel/trastuzumab and then trastuzumab maintenance.

Breast Cancer Update Think Tank Issue 1, 2008

DR HUDIS: I would treat an older patient with a 2-cm, HER2-positive, node-negative tumor conventionally with AC/taxane/trastuzumab, if she were interested and willing.

DR GRALOW: The studies support an anthracycline-and taxane-containing regimen that is more aggressive than I want to administer. However, docetaxel/carboplatin/trastuzumab (TCH) is a tough regimen. Even though the patient might experience less cardiotoxicity, I believe that you trade it for other toxicities. I would try to enroll an older patient in our Phase II trial of weekly paclitaxel/trastuzumab, but I don’t have data to do that off study. Off study, I would probably use AC/weekly paclitaxel with trastuzumab.

DR MACKEY: Off study, I would offer a patient like this TCH. I believe that the anthracyclines are a major confounding problem with the cardiotoxicity that we see with trastuzumab. I have found that TCH is reasonably well tolerated.

DR ROBERT: I was involved with BCIRG 006, and we’ve prescribed a fair amount of TCH. I believe that we find some comfort in using less chemotherapy. So off study I would administer TCH, but I wouldn’t be wedded to six cycles.

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Breast Cancer Update Issue 1, 2008

DR GEYER: The statistical design for BETH is chemotherapy with trastuzumab with or without bevacizumab, and the protocol basically provides for two chemotherapy regimens. One is the TCH regimen that was used in the BCIRG 006 trial.

The other regimen uses docetaxel at 100 mg/m² every three weeks times three cycles followed by FEC with the epirubicin at 90 mg/m². Patients on the docetaxel/FEC regimen receive the targeted therapy with the docetaxel. It is suspended during FEC and then resumed after FEC. Obviously, the targeted therapy with TCH begins concurrently with the chemotherapy in both arms. All patients entered through the CIRG and NSABP will receive TC. The idea of the two arms and the TCH justification arrive from the current results that Dr Slamon presented at the 2006 San Antonio meeting showing that outcomes with TCH versus ACTH were statistically indistinguishable. The confidence intervals overlapped tremendously, and no statistically discernible difference in efficacy is apparent at this point, with a substantial number of events already reported.

The other compelling part of the 006 trial relates to the cardiac toxicity issue. All the trials with trastuzumab after anthracyclines have shown a low tolerable rate of cardiac dysfunction, but clearly the lowest cardiotoxicity rates of any of the trials were seen on the TCH arm. So I believe the TCH is showing efficacy on a similar magnitude to the anthracycline and does have a more favorable safety profile.

Breast Cancer Update Issue 2, 2008

DR STEPHEN E JONES: The issue of adjuvant trastuzumab without chemotherapy in older or frail women does come up, and it makes sense, particularly for a woman with hormone receptor-positive breast cancer with whom you are planning to use an aromatase inhibitor. Although data from the TAnDEM trial of anastrozole with or without trastuzumab for patients with hormone receptor-positive, HER2-positive metastatic breast cancer were disappointing, they are open to interpretation.

Most patients with HER2-positive tumors tend to express ER at lower levels. These are not patients who we expect to respond well to endocrine therapy. My interpretation is that approximately 20 percent of patients fared well, even at three years, and were still responding to both the aromatase inhibitor and trastuzumab.

That subpopulation of patients with relatively indolent, HER2-overexpressing — probably ER-positive and PR-positive — breast cancer may fare well. Having said that, some older women will refuse chemotherapy. In those instances you have to consider trastuzumab monotherapy.

Breast Cancer Update Think Tank Live 2007

DR O’SHAUGHNESSY: I have treated healthy older patients, even women with T1 tumors, with the combination of trastuzumab and chemotherapy. As for adjuvant trastuzumab alone in the elderly, I can only think of one case — an 88-year-old woman with a node-positive, HER2-positive tumor whom I treated with capecitabine and trastuzumab. She didn’t tolerate the capecitabine well, so I used an aromatase inhibitor and trastuzumab.

I am currently treating a patient who is in her late seventies with a favorable tumor — T1N0, ER-positive — with weekly paclitaxel and trastuzumab, and she is faring well. As patients age, they are delicately balanced, so we’re increasingly concerned about harming them and I won’t use doublet chemotherapy with trastuzumab.

I haven’t tried nab paclitaxel with trastuzumab in the adjuvant setting, but it’s a thought for patients who are diabetic or are weak in the muscles, for whom steroid premedication is a problem.

Meet The Professors Breast Cancer Issue 1, 2008

DR GRALOW: I would love to feel comfortable administering antiestrogen therapy along with trastuzumab and omitting the chemotherapy, but I have to say that I believe in the synergy between trastuzumab and chemotherapy, and I also believe that the combination is better than trastuzumab alone.

If I truly felt that I couldn’t administer chemotherapy, with no study to back me up, I would do that. But I think that if she could handle a taxane, that would be my preference. Also, sometimes for patients like this I’ll say, “Let’s try it and see how it goes. If we have to stop the chemotherapy after one or two cycles, then at least we’ve tried it and now we know.” I believe the regimen that has the most data to back it up would be docetaxel/carboplatin/trastuzumab.

I do believe the data are good, if I’m doing something off study and I’m altering tested regimens anyway, in terms of the synergy between paclitaxel and trastuzumab.

Weekly paclitaxel is much more tolerable, especially in an elderly population, than the classic TCH regimen.

So I’m going totally off what the studies have shown, searching for a regimen that I think she can tolerate and one that makes sense. I might lean toward weekly paclitaxel with trastuzumab.

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