In Breast Cancer, Delay Between Surgery and Chemo Harms Survival

Liam Davenport

July 29, 2019

A delay in starting adjuvant chemotherapy after surgery for breast cancer can adversely affect survival, say US researchers, who found that the type of surgery performed plays a significant role in that delay.

In particular, the team found that for women who underwent reconstruction following mastectomy, there was more likely to be a delay before starting adjuvant chemotherapy longer than the 120 days currently recommended.

This, crucially, could have an impact on survival, they warn, because a delay from diagnosis to chemotherapy of more than 120 days was associated with a 29% reduction in overall survival.

The research was published online by the Annals of Surgical Oncology on July 22.

These findings "confirm that timely care is important for breast cancer patients and should be considered in their treatment plan," commented lead author Judy C. Boughey, MD, professor of surgery and a surgical oncologist at the Mayo Clinic, Rochester, Minnesota.

Overall, the results are "encouraging [in] that 89% of women who are recommended chemotherapy postoperatively do get it within 120 days of their diagnosis, but there is still room for improvement," she said.

She recommended that hospitals examine whether they can reduce the interval from breast cancer diagnosis to surgical procedure.

Delays, Boughey noted, could be due to poor access to care, longer wait times for a second opinion, and the coordination between surgeons needed to organize immediate breast reconstruction.

The authors point out that not only is timeliness in the delivery of cancer care a concern for patients and physicians on a subjective level but also that there is "a growing body of data" to suggest that it affects outcomes.

Although previous studies were inconclusive or found no correlation between the timing of breast cancer care and overall survival, more recent studies have shown that long delays have detrimental effects.

This led to a recommendation by the American College of Surgeons' Commission on Cancer to include the administration of systemic chemotherapy within 120 days of diagnosis as a quality metric for the treatment of some women with breast cancer.

Study Details

For their study, Boughey and colleagues used the National Cancer Database to identify patients with stage I–III breast cancer who underwent surgery and who received adjuvant chemotherapy between 2010 and 2014.

They included 172,043 women, of whom 90,488 (52.6%) underwent breast conservation, and 81,555 (47.4%) underwent mastectomy.

Of the mastectomy patients, 46,253 (56.7%) did not undergo immediate reconstruction, and 35,302 (43.3%) did undergo immediate reconstruction. Contralateral prophylactic mastectomy (CPM) was performed in 31,615 women (38.8%).

The median time from diagnosis to surgery was 27 days. The time frame was significantly shorter for women who underwent breast conservation than for those who underwent mastectomy, at 25 days vs 29 days (P < .001).

Among women who underwent mastectomy, the median interval to surgery was longer for those who underwent reconstruction than for those who did not, at 35 days vs 26 days (P < .001).

CPM was also associated with a slight but significant increase in the median time to surgery, at 31 days, vs 29 days for women who underwent therapeutic mastectomy only (P < .001).

Although there were differences in the time from surgery to chemotherapy between surgical groups, the team described the differences as "small and not clinically significant." The median ranged from 43 to 44 days across the study population.

The overall median time from diagnosis to chemotherapy was 74 days. For 89.5% of patients, chemotherapy was initiated within 120 days.

Again, breast conservation was associated with a shorter overall time to chemotherapy, at 71 days, vs 78 days for mastectomy (P < .001). Fewer patients began receiving chemotherapy more than 120 days after diagnosis, at 8.3%, vs 12.9% (P < .001).

Immediate reconstruction following mastectomy was associated with a longer time to chemotherapy compared to not undergoing reconstruction, at 84 days vs 74 days (P < .001).

The delay in receiving chemotherapy was greater than 120 days in 15.0% of mastectomy patients who underwent immediate reconstruction and in 11.3% of those who did not (P < .001).

Interestingly, tissue-based reconstruction was associated with a higher percentage of patients experiencing a delay to chemotherapy beyond 120 days compared with those who underwent implant-based reconstruction, at 16.0% vs 13.3% (P < .001).

Further analysis indicated that a delay of more than 120 days in receiving chemotherapy was less common for patients with triple-negative breast cancer than for those with HER2-positive or hormone receptor–positive/HER2-negative cancers, at 7.4% vs 10.3% and 11.6%, respectively.

A delay was less likely for patients with stage I or II disease.

Patient factors linked to a delay from diagnosis to chemotherapy were increasing age, higher comorbidity score, being black, and having a primary payor other than private insurance.

Taking these factors into account, reconstruction after mastectomy remained significantly associated with chemotherapy delay on multivariate analysis, at an odds ratio of 1.71.

The median follow-up time was 46 months.

The team calculated that a chemotherapy delay of more than 120 days was associated with worse overall survival compared to a delay of 120 days or less, at a hazard ratio of 1.29 (P < .001).

This equated to an adjusted estimate of 5-year overall survival of 88.6% for patients with a chemotherapy delay of more than 120 days, vs 91.9% for women with a shorter delay.

This ranged from a hazard ratio of 1.47 in patients with HER2-positive disease to 1.23 in those with triple-negative breast cancer and 1.23 in women with hormone receptor–positive/HER2-negative disease.

The study received no external funding. Three coauthors received salary support from the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery. The other authors have disclosed no relevant financial relationships.

Ann Surg Oncol. Published online July 22, 2019. Abstract

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