SALT LAKE CITYWomen 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
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
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.