Stopping Smoking May Increase Breast Cancer Survival

SALT LAKE CITY—Women who continue to smoke during treatment for early breast cancer have more than double the risk of death, compared with those who have never smoked or those who quit the habit before their treatment, according to a study presented at the 45th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO abstract 2024).

"We knew that smoking is a risk factor for developing breast cancer, but it was unclear how smoking history influenced treatment outcomes. That was the impetus for the study," lead author Khanh Nguyen, MD, told ONI in an interview.

Dr. Nguyen, a radiation oncologist at Fox Chase Cancer Center, Philadelphia, and his colleagues retrospectively analyzed outcomes according to current and past smoking status in 1,900 women who underwent breast-conserving surgery and radiation therapy for breast cancer between 1970 and 2002.

The majority of the study population, 1,039 women, had never smoked (nonsmokers). Among the 861 women who had ever smoked (any-smokers), 329 stopped smoking before treatment (past smokers) while 75 continued to smoke during treatment (current smokers).

Women in the different groups were similar with respect to age, race, menopausal status, T stage, nodal status, margin status, hormone-receptor status, method of detection, hemoglobin levels, and receipt of chemotherapy and hormonal therapy. However, a significantly larger proportion of any-smokers than of nonsmokers received tamoxifen (42% vs 37%, P = .0485). This difference was further magnified when comparing past smokers to nonsmokers for tamoxifen use, with 52% of past smokers being on tamoxifen, compared with 37% of nonsmokers (P < .0001).

The investigators assessed treatment outcomes during a median follow-up of 65 months. In univariate analyses, compared with nonsmokers, past smokers had significantly higher rates of cause-specific survival (93% vs 81%) and overall survival (80% vs 68%); however, rates were similar after adjustment for tamoxifen use. Compared with nonsmokers, any-smokers had significantly lower rates of freedom from distant metastases (81% vs 87%) (see Figure 1) and cause-specific survival (78% vs 86%) (see Figure 2).

In multivariate analyses, current smoking was associated with a significant increase in the risk of death from any cause (hazard ratio, 2.558), but past smoking was not associated with an elevated risk. With respect to other outcomes, smoking status did not influence the risk of death from breast cancer or the risks of developing an ipsilateral recurrence, a contralateral breast cancer, a nonbreast second cancer, or distant metastases.

The findings generally confirm a long-held suspicion that smoking has a detrimental effect on treatment outcomes in women with breast cancer, Dr. Nguyen said. "The encouraging finding is that past smokers have the same outcomes as nonsmokers, meaning that if patients had a smoking history and they quit, they were likely to do as well as nonsmokers," he added.

Three hypotheses have been proposed to explain why smoking might adversely affect outcomes of cancer treatment, Dr. Nguyen said. One hypothesis is that smoking causes hypoxia in the tumor bed, rendering radiation therapy less effective. A second is that the chemicals in smoke may alter the gene expression of the cancer, making it more aggressive, more resistant to treatment, and more prone to spread. And a third hypothesis is that ongoing smoking simply translates into continued exposure to its carcinogenic effects.

"It’s never too late to try to help patients to quit, especially before they start treatment," Dr. Nguyen said. He noted that the best area for future research might be effective interventions for promoting smoking cessation. "Not all patients have the same response to smoking cessation programs, and it has to be individualized. The emphasis should be on how best to get patients to overcome their smoking habit," he said.

To place the findings in context, Dr. Nguyen compared smoking cessation with other measures aimed at improving breast cancer survival. "This might get me in trouble with the chemotherapists, but current chemotherapy standards improve survival maybe by 5% or 10%. By promoting smoking cessation, we have a great opportunity to make a tremendous difference in terms of helping improve survival," he said.