In the node negative group, it’s a little more difficult to figure out but a conservative answer at this point in time, and this is changing kind of year by year, tumors more than a centimeter plus some other risk factor such as being ER/PR negative or having a high S phase, some people would say being HUR2 positive, even if they ER/PR positive, would make people treat them. Some people add in grading so if they’re poorly differentiated or moderately differentiated and have another one of these risk factors such as having a high S phase, they would give them systemic adjuvant therapy.

The choices for systemic adjuvant therapy, for estrogen receptor and progesterone receptor positive patients who are postmenopausal, hormone therapy can be as effective an adjuvant therapy as combination chemotherapy. For ER negative patients, combination chemotherapy is superior to hormone therapy and for all premenopausal women, regardless of their ER/PR status, combination chemotherapy is superior to hormone therapy. But hormone therapy may have a further additive benefit and those patients you may consider combined therapy. So chemotherapy is used for all premenopausal women and those postmenopausal women whose tumors are not much affected through hormonal manipulation.

Hormone therapy is useful for estrogen receptor positive postmenopausal women and my bent, and I think this is increasingly popular, is those women at low risk. So postmenopausal women, even if they’re ER positive with a number of positive nodes or other high risk factors, you may consider giving them chemotherapy then followed by hormone therapy. Premenopausal women who are ER positive would also be considered for chemotherapy then followed by tamoxifen. I don’t use tamoxifen and chemotherapy together and I don’t think most people do. It does increase your risk for clotting complications. If you sequence the therapy, it’s as effective and it avoids some of those clotting combinations. People clot on chemotherapy and they also have an increased risk for clotting on tamoxifen.

Adjuvant chemotherapy increases disease free survival more than overall survival. What that says is it just pushes back the time for relapse. In some patients it doesn’t actually cure them but in some patients it does absolutely cure them and you do add to quality life and you also do add to the bottom line a number of patients cured though not as many maybe as we’d like.

It’s clear you need more than one drug for adjuvant therapy and it’s increasingly clear that it’s much better to give good, high doses of chemotherapy over a short period of time than to string long doses over long periods of time and nobody should be getting adjuvant therapy for twelve months or more. Most adjuvant therapy is given over 12 weeks to 6 months, in that range.

This looks at patients given different doses of Cytoxan and Adriamycin 5-FU and this solid line, in terms of disease free survival and overall survival are those patients who are more aggressively dosed than patients who are given a lower dose. Dose does matter. Dose over time or dose intensity is a predictor for outcome.

These look at HUR2-nu expression and if you overexpress HUR2-nu, those patients who were HUR2 negative, they seem to fair pretty well whether they got high doses of chemotherapy or low doses of chemotherapy. But if you were going to get cured, you had to get high doses of chemotherapy if you overexpressed HUR2-nu. So I think HUR2-nu is a predictor for outcome. It also tells you how you have to treat patients. There’s also increasing information that hormone therapy is not useful for patients who overexpress HUR2-nu or their tumors overexpress HUR2-nu and that CMF probably isn’t very useful and that you need to use Adriamycin in good doses.