Published: 18-10-2023 14:10 | Updated: 18-10-2023 14:17

Epidemiological studies on breast cancer risk factors and screening

A new thesis from Karolinska Institutet focuses on cancer prevention by investigating the factors and outcomes associated with false-positive mammography recalls, a fairly common event where women are called back for additional tests after an initial screening, but no cancer is detected during the follow-up. A second aim of the thesis was to further our understanding of the association between breast cancer risk factors in women and cancer risk among their relatives, particularly sisters.

Portrait of PhD student Xinhe Mao
Xinhe Mao. Photo: Gunilla Sonnebring

In her thesis, PhD student Xinhe Mao at the Department of Medical Epidemiology and Biostatistics, provides information for both screening processes and genetic counseling. Her results may aid in future tailoring of individualized surveillance plans for women with a false positive recall.

What are the most important results in your thesis?

“My thesis includes four different studies with focus in study I-II on factors associated with false positive (FP) mammography recalls and then the risk of subsequent breast cancer among women with a FP mammography recall. In Study III, we investigated if established breast cancer risk factors in women were associated with their sisters' breast cancer incidence and in Study IV, we delved into genetic risk factors and investigated the associations of both carriership of protein-truncating variants (PTV) in eight genes and breast cancer polygenic risk scores (PRS) in women, with the risk of cancers in their first-degree relatives.

What we found was that several breast cancer risk factors were associated with an FP recall. However, none are suitable for interventions aiming to reduce FP recalls due to the potential risk of missing actual tumours. We observed a long-term increased breast cancer risk following a FP recall, with the risk being higher in older women, women with lower mammographic density, and within the first few years after the FP recall. These findings should be useful to assist in customizing a personalized surveillance program for women with a FP recall.

Further, my study results suggest that women’s breast density and breast cancer risk scores — information that becomes available at screening — may be useful for estimating the breast cancer risk in their sisters. Additionally, PTVs in non-BRCA genes might provide a better understanding of cancer clustering within families.”

Why did you become interested in this topic?

“Breast cancer is the most common cancer among women worldwide. In Sweden, 1 in 9 women is diagnosed with breast cancer during their lifetime. In developed countries, mammography screening is relevant for all women over a certain age (in Sweden, the recommended age is 40 and above). Therefore, contributions to this field are potentially meaningful for a vast number of women.“

What do you think should be done in future research?

“Mammography screening contributes to a reduced breast cancer mortality rate. However, there's still room for further study and enhancement. For instance, women diagnosed with breast cancer through screening programs typically exhibit smaller tumor sizes, lower grades, and more favorable tumor characteristics compared to other breast cancer patients. Yet, not every woman participates in the screening each time she's invited. Given this context, we are keen to analyze if tumor characteristics or prognosis differ among those with screen-detected breast cancer, based on their screening history.”

Doctoral thesis

Epidemiological studies on breast cancer risk factors and screening

Xinhe Mao. Karolinska Institutet (2023), ISBN: 978-91-8017-110-6