Edited comments by Dr Singletary

Risk assessment in clinical practice

I don’t think surgeons use risk assessment on a routine basis. While they may be aware of the risk assessment tools, these are not being formally incorporated into practice or being routinely documented in the medical record. Any woman over age 35 should have a risk-factor history taken, and, if she appears to have elevated risk, she should be asked if she would like her five-year and lifetime risks calculated using the Gail model. Most women tend to overestimate their risk, so for many, risk assessment will provide some reassurance.

When we look at the option of chemoprevention with tamoxifen, we need to always weigh the benefits versus side effects. Certainly for young women at high risk, tamoxifen has far more benefits than risks. Many women have heard about the side effects but do not understand the results of the P-1 trial showing the 49% reduction in breast cancer risk.

The role of ductal lavage in a clinical risk management strategy

Ductal lavage is a fairly simple technique that is not very timeconsuming and can be incorporated in a surgical or medical practice without any difficulty. We actually have our research nurse perform our ductal lavage procedures. It’s well tolerated by the patients, and we have not had any patients complain of discomfort.

Ductal lavage can be offered to patients if the cytologic information would help them in their risk management decision-making process. It may help patients who are considering tamoxifen but unsure about whether to take it. Lavage provides a physician and patient with more information to round out the risk profile. The presence of atypical cells may be enough to encourage a woman to take tamoxifen or consider participating in a chemoprevention study. These ductal lavage findings may help put the side effects of tamoxifen into perspective. Not finding atypical cells does not necessarily decrease their risk, as we do not know the meaning of a negative ductal lavage.

The Risk Assessment Working Group developed a risk management strategy, dividing patients into three risk categories: average risk, elevated or high risk, and very high risk. The algorithm targets the moderate to very high risk groups and addresses the issue of where ductal lavage would be incorporated. Essentially, it would be for women in whom information from the ductal lavage would influence their decision-making.

Recently published management algorithms:

Morrow M et al. Evaluation and management of the woman with an abnormal ductal lavage. J Am Coll Surg 2002; 194(5): 648-656. No abstract available.

O’Shaughnessy JA et al. Ductal lavage and the clinical management of women at high risk for breast carcinoma. Cancer 2002:94(2):292-298. Abstract

Relationship between atypical cytology and atypical ductal hyperplasia

A finding of atypia on ductal lavage may put a woman at the same risk as finding atypical hyperplasia on a tissue biopsy — four- to five-fold increased risk.

If we look at the P-1 data, women with atypical ductal hyperplasia received the most benefit from tamoxifen, with an 86% reduction in breast cancer risk. We cannot say that atypical cytology is the same as atypical ductal hyperplasia, but there may be some relationship.

The best data we have is from Carol Fabian’s fine-needle aspiration study* in which she did four quadrant periareolar aspirations. She showed that women with atypical cells had a 15% risk of breast cancer within a short time, especially in those patients who also had an elevated Gail risk. We cannot say that atypical cytology is equivalent to atypical hyperplasia on a tissue biopsy, but it seems to be in the same ballpark figure of increased risk.

*Fabian CJ et al. J Natl Cancer Inst 20001;92(15):1217-27. Abstract

Incorporating the ATAC outcomes into clinical practice

We are now going to use anastrozole at MD Anderson as firstline adjuvant endocrine therapy for postmenopausal women with node-positive, estrogen receptor-positive disease. We think that the side effects may be slightly less than tamoxifen, and there was a modest disease-free survival advantage. This decision was reached among our medical oncologists, surgical oncologists and radiation oncologists.

I think anastrozole will eventually also move into the nodenegative setting and perhaps also be used in clinical trials of ductal carcinoma in situ. Anastrozole has a good safety profile, and I believe that surgeons will be very comfortable prescribing this agent.