Expert Urges Further Study of Timing in Breast Cancer Surgery

NEW YORK--There is sufficient evidence that the timing of breastcancer surgery affects outcome to warrant further inquiry, WilliamJ. Hrushesky, MD, said at the 14th Chemotherapy Foundation Symposium.

It is known that tumor growth rates wax and wane during the femalemenstrual cycle, but many questions remain that can be answeredonly by rigorously designed studies, said Dr. Hrushesky, seniorattending oncologist, Stratton VA Medical Center, and professorof medicine, Albany Medical College.

In his research in both mice and women, Dr. Hrushesky has foundthat cellular immune function and/or host resistance to cancergrowth and spread vary with the reproductive cycle stage. Tumorgrowth rate is slowest during the early luteal stage, which typicallyoccurs in the first quarter of the cycle after ovulation, a timewhen the immune response is most robust. It is this stage thatappears to be optimal for resection, he said.

"In our own initial clinical series, women resected duringthe middle of the menstrual cycle proved to have a fourfold betterchance of surviving 10 years than those whose breast cancers wereresected during or nearer to menses," he said. Ten otherretrospective studies have confirmed this finding, and multivariateanalyses demonstrate that timing is an independent predictor ofboth breast cancer recurrence and death, he added.

Does that mean that all breast cancer surgery should be scheduledfor the early luteal phase? Not at this time, Dr. Hrushesky said."Many meaningful uncertainties remain, and only rigorousstudy can answer them. We need to clarify the impact of resectiontiming and the size of the window of opportunity--when it opensand closes."

He added that we further need to understand the underlying biology"because a full understanding of the mechanisms may leadto neoadjuvant hormonal strategies to enhance the control of thisand other cancers"

Determine Actual Cycle Phase

A well-designed study must be randomized to remove any bias inoperative timing within the menstrual cycle, Dr. Hrushesky said.Further, when more than one operation is performed, temporal coordinationof surgical procedures is essential so that all occur at the samepoint in the patient's cycle. And, of great importance, the actualphase of the cycle must be determined as exactly as possible throughhormone measurements and endometrial aspirations.

A handful of prospective studies have been planned, he said, butnone, in his view, are adequately designed, and several were abandonedfor lack of funding.

He estimates that with 60,000 cycling women diagnosed with breastcancer in the United States every year, the lives of as many as400,000 may have been negatively impacted in the decade sincethese questions have been asked and left unanswered. He baseshis estimate on the assumption that, with random distributionof surgical scheduling, only one quarter to one third of all cyclingwomen undergo resection at an optimal time.

Dr. Hrushesky urged physicians, advocacy groups, and other interestedparties to press for adequate studies. He asserted that sinceproper timing of an operation is a low-tech, no-cost matter, itis difficult to justify delaying clinical studies designed todefinitively answer questions about the nature and mechanismsby which the menstrual cycle impacts the outcome of breast cancersurgery. "It is urgent that we replace our ignorance in thisarea with knowledge that could save thousands of lives every year,"he said.