Poor Screening Adherence May Worsen Breast Cancer Outcomes

Liam Davenport

December 11, 2017

SAN ANTONIO ― Rates of participation in mammography screening programs may be decreasing, which may in turn increase the risk that women will not follow their breast cancer treatment and may thus experience worse outcomes, the results of two European studies suggest.

From a survey of almost 1300 women, Jean-Francois Morere, MD, PhD, Hôpital Paul Brousse, Villejuif, France, and colleagues found that, compared with previous years, there was a significant drop in adherence to mammography screening in 2016, particularly in women aged 50 to 54 years and in those who are unemployed.

Describing these particular decreases as "disturbing," the team said: "Although organized programs have been shown to ensure equitable access to cancer screening, this achievement remains precarious and requires regular monitoring."

In a separate study that examined the consequences of not taking part in screening, Wei He, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, and colleagues compiled data from several registries on more than 5000 women who had been diagnosed with invasive breast cancer.

Dr Wei He

This study, presented, like the first, as a poster at the San Antonio Breast Cancer Symposium (SABCS) 2017, showed that nonparticipation in screening was associated with delayed surgery, discontinuation of adjuvant therapy, and, ultimately, worse disease-free survival.

The authors write: "Our study provides, for the first time to our knowledge, evidence that the worse survival observed among screening nonparticipants is partly due to treatment nonadherence; thus is modifiable after cancer diagnosis."

Participation in France

For the first study, Dr Morere and his team analyzed the EDIFICE surveys, which have been conducted in France since 2005, to examine the extent of participation in screening programs and factors associated with treatment compliance.

The fifth EDIFICE survey, which is the most recent, involved a representative sample 657 women aged 50 to 74 years who had no history of cancer and who completed telephone interviews in late 2016.

The women were asked about breast cancer screening and the date of their last examination. The team also collected demographic data on social characteristics and socioprofessional characteristics (SPC), and assessed social vulnerability using the EPICES score.

The results showed that compliance with breast cancer screening decreased significantly since 2015, the year of previous EDIFICE survey, falling from 81% to 75% in 2016 (P = .02).

Both years represent a decrease from the peak of 83% recorded in 2008 and 2011.

The team also found that social vulnerability had a significant impact on compliance with screening (P < .01), which was not seen in the 2011 and 2014 surveys.

The rate of compliance in 2016 was 65% among vulnerable people, vs 76% in 2014 (P = .04); it was 79% in nonvulnerable women in 2016, vs 85% in 2014 (P = .04).

For the first time, the researchers showed that there was a decrease in compliance with screening among women aged 50 to 54 years, falling from 88% in 2014 to 74% in 2016 (P = .01), and that age had a significant effect on compliance (P = .02).

Although SPC was found to have no overall effect on compliance with screening, there was a significant reduction in compliance among unemployed people in 2016 compared to 2008, at 73% vs 81% (P = .03).

Outcomes Among Nonparticipants in Sweden

In the second study, the researchers explored potential explanations for the poor survival seen in women who did not participate in mammography screening programs. They examined whether compliance with breast cancer treatment was lower in such women.

The researchers gathered data from the Stockholm Mammography Screening Program and linked those data to the Stockholm-Gotland Breast Cancer Register, the Swedish Prescribed Drug Register, and the Cause of Death Register.

From this, they identified 5107 women from Stockholm who had been diagnosed with nonmetastatic invasive breast cancer between 2001 and 2008 and prospectively followed them with respect to treatment and survival through 2013.

Of those women, 4497 were included in the delayed-surgery (≥6 weeks) analysis, 1974 were included in the adjuvant hormone therapy analysis, and all 5107 were included in the disease-free survival analysis.

Women were considered to be nonparticipants in mammography screening if they had been advised to undergo screening within 2 years of their being diagnosed with breast cancer but had not done so.

In the late-surgery multivariable analysis, 17.4% of the women were screening nonparticipants. They were at significantly increased risk of having late surgery than screening participants, at an adjusted odds ratio on multivariate analysis of 1.86 (90% confidence interval [CI], 1.50 - 2.32).

For the adjuvant hormone therapy multivariable analysis, 17.2% of the women were screening nonparticipants. Those patients were at significantly increased risk for discontinuation of therapy compared with participants, at a hazard ratio (HR) of 1.30 (90% CI, 1.10 - 1.54).

Multivariable analysis also revealed that for screening nonparticipants, disease-free survival was significantly worse (HR, 1.18; 90% CI 1.01-1.39). The analysis took into account tumor characteristics and other variables.

A similar picture was seen when the researchers correlated screening nonparticipants with screen-detected cancers and interval cancers. They found significantly increased risks for late surgery and discontinuation of adjuvant hormone therapy and significantly worse disease-free survival.

The team is now planning to examine whether interval cancers are associated with worse survival in screening nonparticipants, after taking into account compliance with breast cancer treatment.

Talking to Medscape Medical News, Dr Wei said that the current study cannot speak to the reasons underlying lack of participation in screening programs, and that further studies are necessary.

He believes that the steps needed to increase participation in screening will vary from country to country.

He said: "For example, in Sweden, we have a very unified health system, so the financial problem won't be a big problem, but in some other countries, providing the service for free will increase the screening rate dramatically."

Other measures to increase participation, Dr Wei noted, include education and awareness, as well as ensuring that there are screening facilities outside of the main centers.

"If the woman lives very far away from the screening center, this will dramatically reduce the likelihood of participation, so smaller hospitals have to ensure that they can provide an equal service," he said.

Independent Thoughts

Approached for comment, Deborah J. Rhodes, MD, professor of medicine at the Mayo Clinic, Rochester, Minnesota, said that in the United States, the rate of participation in mammography screening did not changed substantially between 2005 and 2015.

Recent data from the National Center for Health Statistics nevertheless suggest that participation in screening is lower in the United States than in France, with 65.3% of women aged ≥40 years having had a mammogram in the past 2 years.

"However, like the French data, mammography adherence is lower in women 40 to 49 than in older women," she said.

"Current US guidelines recommend either not screening average-risk women in this age group or screening them less frequently, as compared with earlier guidelines," Dr Rhodes pointed out.

She noted that this is because breast cancer is less common in this age group and that "mammography is considerably less effective...because younger women are more likely to have dense breasts, which can contribute to masking of cancers by dense tissue."

Dr Rhodes said: "My observation is that the changing and differing guidelines are certainly causing confusion among women, even if that is not, as of yet, reflected in declining adherence rates in the US.

"I do recommend mammography annually to my patients age 40 and older, but I also stress the limitations of mammography and the importance of reporting any breast changes, even in the setting of a recent negative mammogram."

She also considers supplemental screening if the breast tissue is dense and recommends complying to high-risk guidelines for MRI screening if applicable risk factors are present.

"Ultimately, I hope we will move towards more individualized screening, based on breast density and also on biologic markers of increased risk, which may come from a variety of sources, including genetic tests, imaging biomarkers of risk, etc," Dr Rhodes said.

She also said that the Swedish study is "very interesting."

"It has always been assumed that women with mammography nonadherence have poorer breast cancer treatment outcomes because of delayed diagnosis, but this study suggests there are other contributing factors, including delay in surgery and discontinuation of endocrine therapies."

Noting the lack of data on associations involving socioeconomic status, Dr Rhodes nevertheless said: "You can't help but wonder if the mammography nonadherers have poorer access to healthcare in general, not just screening, but surgery and medications."

She added: "This a very important area for further study."

The investigators have disclosed no relevant financial relationships.

San Antonio Breast Cancer Symposium (SABCS) 2017: Posters P6-08-07 and P6-08-20, presented December 9, 2017.

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