I would order an Oncotype DX assay for this 40-year-old premenopausal woman. I believe it allows us to further understand the biology of early-stage hormone-driven breast cancer. The exception would be for a patient who is not a candidate for chemotherapy, but those patients are few and far between. I order the assay even for patients to whom I’m concerned about administering chemotherapy so that I can have a more precise discussion with them.

I would continue tamoxifen for this 40-year-old premenopausal woman with a node-negative IDC. The data from the ATLAS trial supported those from the MA17 study and showed that extended endocrine therapy is better. I use the analogy of high blood pressure and tell patients that if their blood pressure were under control they would not stop treatment unless they were experiencing side effects. The treatment of early-stage breast cancer is similar.

I would recommend an Oncotype DX assay for a 40-year-old premenopausal woman with a 1.5-cm, node-negative, ER-positive, HER2-negative IDC. My general approach is not to order this assay for patients with T1a tumors. For a patient with a T1b tumor, I would feel out the patient’s level of anxiety and determine her personal take on it. This is a gray area, and factors like the lower tumor grade and the expression levels of hormone receptors would come into play. I also don’t consider the assay for T3 tumors unless I have a compelling reason for not administering chemotherapy.

I would have a conversation with a 40-year-old patient with low-risk Stage I cancer about 5 more years of tamoxifen therapy, but I wouldn’t push it. If the patient is tolerating tamoxifen well, I suggest that continuing for an additional 5 years is a reasonable option. But for patients who have struggled with hot flashes and are not tolerating tamoxifen well, I would advise them to stop. The results of the recent aTTom trial confirmed the results of the ATLAS study, which showed a benefit to continuing tamoxifen for an additional 5 years.

For a 40-year-old patient with a node-negative, ER-positive IDC, I would recommend an Oncotype DX assay.

I’d stop tamoxifen for the 40-year-old premenopausal woman with a node-negative IDC. Although the aTTom and ATLAS trials are positive for longer-duration tamoxifen therapy, the absolute survival difference is on the order of 3%, which means that the majority of women don’t benefit from longer therapy. The results of the studies were not broken down according to whether patients had node-negative or node-positive disease. In a lower-risk, node-negative population, I believe that the benefit will be less than 3%.

If a patient’s risk of recurrence increased with 1 or more positive nodes, I’d have a discussion with the patient and lean toward continuing therapy. If the patient were experiencing a lot of symptoms or problems from tamoxifen, I would still consider stopping therapy.

I would order an Oncotype DX assay for the 40-year-old premenopausal woman.

For patients with node-negative disease, the main reason I would order an Oncotype DX assay is to make a decision on the utility of chemotherapy followed by hormone therapy. If a patient insisted that she would not receive chemotherapy, I would not order the test. Conversely, for a patient who insisted on chemotherapy, I would not recommend the test.

We now have 2 retrospective studies that suggest that the Oncotype DX assay is not merely prognostic but is also predictive for the marginal benefit of chemotherapy. The threshold for where you draw the line in terms of the chemotherapy benefit varies a little. The commercial test considers scores above 31 to be high risk and scores of 18 to 31 to be intermediate, whereas the TAILORx study uses a lower threshold of 11 to 25. The current RxPONDER trial in node-positive disease is for patients with Recurrence Scores^® of 25 or lower. Those with scores above 25 receive chemotherapy. I generally follow the guidelines that were established in the clinical trials for my daily practice. I would be a little more biased toward chemotherapy for younger patients.

I would continue tamoxifen for the 40-year-old patient with negative nodes. We now know from both the aTTom and the ATLAS studies that 10 years of tamoxifen is associated with reduced mortality from breast cancer. The results of the MA17 study showed that 10 years of hormone therapy in node-positive disease is associated with reduced mortality from breast cancer. Whereas the aTTom and ATLAS studies evaluated the efficacy of 10 years of tamoxifen specifically, the MA17 trial studied the effect of an additional 5 years of letrozole after treatment with 5 years of tamoxifen. The MA17R trial will answer the question of whether 10 years of AI therapy is better than 5 years.

I believe it’s a question of how you view the data. If you’re a narrow constructionist, you conclude that 10 years of tamoxifen is better than 5 for premenopausal patients who are candidates for tamoxifen. If you’re strict about it, you might say that 5 years of an AI is sufficient and stop therapy.

I would order an Oncotype DX assay for this 40-year-old patient with a node-negative, ER-positive IDC.

The available data suggest that most patients with a low-risk score should receive hormonal therapy alone. Most patients with a high-risk score and moderate or large tumors (>1 cm) are likely to benefit from chemotherapy followed by hormonal therapy. The difficult question is, how do we manage intermediate-risk disease? Until we have definitive data from the TAILORx study, I believe we have to consider the individual patient and her feelings about chemotherapy and come up with a decision that she is comfortable with.

I would continue tamoxifen in this scenario based on the recent data from the ATLAS and aTTom studies, which support further benefit to continuing tamoxifen for another 5 years. The data were not broken down between patients with node-negative and node-positive disease. Hence, I would have the same recommendation if this patient had node-positive disease.

I would definitely recommend an Oncotype DX assay for this patient. I order the assay whenever my collective decision with the patient about chemotherapy might be affected by the score.

I do end up making a recommendation, but my recommendation is guided by the patient’s preference and what I learn about the patient’s thoughts on relative risks and benefits. If she wanted to be particularly aggressive, I would suggest chemotherapy. I wouldn’t object to ordering an Oncotype DX assay in that situation, but that would be a plan that would vary based on how the conversation with the patient went.

I would recommend that the 40-year-old woman with a 1.5-cm, node-negative IDC continue tamoxifen. We now have data from 2 large, well-conducted trials — the ATLAS and aTTom trials — that showed that patients who received tamoxifen for 10 years experienced a better overall survival than patients who received it for only 5 years. Patients need to be aware of some increased toxicities with longer-duration therapy. However, with the increased survival benefit, I find it difficult to recommend that women who are premenopausal and who have fared well on tamoxifen stop therapy.

For a 40-year-old premenopausal woman with a 1.5-cm, node-negative, ER-positive, HER2-negative IDC, my decision to order an Oncotype DX assay would depend on the tumor biology. I would consider factors such as how strongly positive the hormone receptors were and the Ki-67 staining. I would interpret the Recurrence Score in the context of these other tumor characteristics. If I found adverse features on standard pathologic criteria, I would not order the Recurrence Score because I would administer chemotherapy anyway.

In terms of continuing or stopping adjuvant endocrine therapy, knowing the tumor grade and Recurrence Score would be helpful. If the patient had a Grade I tumor that was strongly ER/PR-positive with Ki-67 staining of less than 10% and a low Recurrence Score, I would be tempted to stop the tamoxifen. If the patient wanted to take a treatment holiday for a year or 2, that would be reasonable. I would await the data on longer-duration AI therapy or wait until she became menopausal and then consider an AI. If the same patient had a Grade II or III node-negative tumor, I would talk to her about continuing tamoxifen. I would discuss the data from the ATLAS and aTTom studies. However, the issue with the results from the ATLAS and aTTom studies is that the benefit did not accrue to patients until after year 10.

I would order an Oncotype DX assay for this 40-year-old patient. Factors like the tumor grade and insurance coverage would influence my decision. If it’s a Grade I tumor and the patient says, “I’m not taking chemotherapy unless you can guarantee I’m not going to die of cancer,” then I won’t order an Oncotype DX assay.

I would discuss treatment options with this 40-year-old patient with a Stage IC IDC. I don’t know enough about her tumor biology to make a definite decision. I would offer the patient the option of continuing tamoxifen and would discuss all treatment options with her in detail.

Data from both the ATLAS and aTTom trials demonstrated a reduction in recurrence with the continuation of adjuvant hormone therapy. However, the ATLAS study was more problematic than the aTTom study because many patients were excluded because of unknown ER status. The data from the MA17 study, which evaluated the effect of extended therapy with an AI after 5 years of tamoxifen, were encouraging and were collected in a more exact way in terms of following patients and using intent-to-treat analysis.