In the JournalsPerspective

Breast cancer diagnosed after negative mammogram has worse prognosis

Breast cancer cases diagnosed after a patient screened negative on a mammogram appeared more likely to be associated with a poor prognosis than those diagnosed following a positive screen, according to a research letter published in JAMA Oncology.

“Approximately 15% of breast cancers are diagnosed after the patient undergoes screening mammography with negative results and before the next recommended screening examination,” Anne Marie McCarthy, PhD, instructor of medicine at Harvard Medical School, and colleagues wrote.

So-called “interval cancers,” diagnosed between examinations, include cancers missed in mammography examinations, in addition to rapid-growing cancers that may have worse prognoses than those detected via screening.

“Identifying women who are at high risk [for] breast cancer with a poor prognosis despite regular screening mammography could enable targeted supplemental screening for women for whom screening mammography may not be sufficient,” McCarthy and colleagues wrote.

McCarthy and colleagues performed an observational study of 306,028 women aged 40 years or older with no breast cancer history who underwent mammography screening between 2011 and 2014. Data on mammography came from the Population-Based Research Optimizing Screening through Personalized Regimens, or PROSPR, consortium, which includes major hospitals in New Hampshire, Boston, Philadelphia and Vermont.

Picture of Mammogram
Breast cancer cases diagnosed after a patient screened negative on a mammogram appeared more likely to be associated with a poor prognosis than those diagnosed following a positive screen
Source: Shutterstock.com

Criteria used to define poor prognosis included distant metastases; cancer-positive regional lymph nodes; ER- and/or PR-positive and HER2-negative invasive cancer with a diameter of 2 cm or more; triple-negative invasive cancer of 1 cm or more in diameter; or HER2-positive invasive cancer at least 1 cm in diameter.

Overall, 272,881 women had a negative screening mammography result and 33,147 had a positive result. Of those with negative results, 160 were diagnosed with an interval cancer.

A greater proportion of cases diagnosed after a negative mammography examination had a poor prognosis than those diagnosed following a positive mammography (43.8% vs. 26.9%; P < .001).

Women who had dense breasts appeared twice as likely to receive a cancer diagnosis, regardless of prognosis, following negative mammography results (OR = 2.07; 95% CI, 1.48-2.89).

Although researchers observed no significant association between age or family history with breast cancer diagnosis following negative mammography result, younger age appeared associated with a worse prognosis among women diagnosed following negative mammography (40 to 49 years vs. 70 to 89 years, OR = 3.52; 95% CI, 1.15-10.72).

“Our results indicate that the positive predictive value of mammography results depends on patient age and family history but not on breast density,” the researchers wrote. “In contrast, the negative predictive value depends on breast density but not on patient age or family history. Although the rate of breast cancer after negative mammography results is small, the likelihood that such cases will be associated with a poor prognosis highlights the need to improve early detection for these women.” – by Andy Polhamus

Disclosures: The authors report no relevant financial disclosures.

Breast cancer cases diagnosed after a patient screened negative on a mammogram appeared more likely to be associated with a poor prognosis than those diagnosed following a positive screen, according to a research letter published in JAMA Oncology.

“Approximately 15% of breast cancers are diagnosed after the patient undergoes screening mammography with negative results and before the next recommended screening examination,” Anne Marie McCarthy, PhD, instructor of medicine at Harvard Medical School, and colleagues wrote.

So-called “interval cancers,” diagnosed between examinations, include cancers missed in mammography examinations, in addition to rapid-growing cancers that may have worse prognoses than those detected via screening.

“Identifying women who are at high risk [for] breast cancer with a poor prognosis despite regular screening mammography could enable targeted supplemental screening for women for whom screening mammography may not be sufficient,” McCarthy and colleagues wrote.

McCarthy and colleagues performed an observational study of 306,028 women aged 40 years or older with no breast cancer history who underwent mammography screening between 2011 and 2014. Data on mammography came from the Population-Based Research Optimizing Screening through Personalized Regimens, or PROSPR, consortium, which includes major hospitals in New Hampshire, Boston, Philadelphia and Vermont.

Picture of Mammogram
Breast cancer cases diagnosed after a patient screened negative on a mammogram appeared more likely to be associated with a poor prognosis than those diagnosed following a positive screen
Source: Shutterstock.com

Criteria used to define poor prognosis included distant metastases; cancer-positive regional lymph nodes; ER- and/or PR-positive and HER2-negative invasive cancer with a diameter of 2 cm or more; triple-negative invasive cancer of 1 cm or more in diameter; or HER2-positive invasive cancer at least 1 cm in diameter.

Overall, 272,881 women had a negative screening mammography result and 33,147 had a positive result. Of those with negative results, 160 were diagnosed with an interval cancer.

A greater proportion of cases diagnosed after a negative mammography examination had a poor prognosis than those diagnosed following a positive mammography (43.8% vs. 26.9%; P < .001).

Women who had dense breasts appeared twice as likely to receive a cancer diagnosis, regardless of prognosis, following negative mammography results (OR = 2.07; 95% CI, 1.48-2.89).

Although researchers observed no significant association between age or family history with breast cancer diagnosis following negative mammography result, younger age appeared associated with a worse prognosis among women diagnosed following negative mammography (40 to 49 years vs. 70 to 89 years, OR = 3.52; 95% CI, 1.15-10.72).

“Our results indicate that the positive predictive value of mammography results depends on patient age and family history but not on breast density,” the researchers wrote. “In contrast, the negative predictive value depends on breast density but not on patient age or family history. Although the rate of breast cancer after negative mammography results is small, the likelihood that such cases will be associated with a poor prognosis highlights the need to improve early detection for these women.” – by Andy Polhamus

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Disclosures: The authors report no relevant financial disclosures.

    Perspective

    Author Name

    Identifying women who will benefit from screening examinations in addition to mammography is an extremely important goal. Although dense breast tissue has been identified as a risk factor for which supplemental screening is frequently performed, not all women with dense breasts require additional testing. This study is a step forward in helping to identify those women who may benefit the most from supplemental screening, which is young women with dense breasts. The Tomosynthesis Mammographic Imaging Screening Trial, or TMIST, and trials of the efficacy of FAST MRI in the setting of dense breasts, may further elucidate guidelines for defining women who need supplemental screening.

    Kathryn Evers, MD, FACR

    Fox Chase Cancer Center

    Disclosure: Evers reports no relevant financial disclosures.