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Women are at higher risk of developing breast cancer if the cancer already occurred in a first-degree or second-degree relative. Up until now, this had only been proven in case of invasive breast cancer. Now, a research team of scientists and physicians of the German Cancer Research Center (DKFZ), the National Center of Tumor Diseases (NCT) Heidelberg, and the University of Heidelberg as well as international colleagues were able to show that the risk of developing breast cancer also rises if precancerous stages were found in relatives. Based on their results, the researchers recommend that women whose relatives have been diagnosed with a preliminary stage of breast cancer should begin early detection of breast cancer.

National Center for Tumor Diseases (NCT) Heidelberg, a joint institution of the German Cancer Research Center (DKFZ), the University Hospital Heidelberg (UKHD) and the German Cancer Aid (DKH).

Breast cancer is one of the most common cancerous diseases in women and the most common cause of cancer-related deaths. Studies have shown that a mammography screening program lowers the mortality of breast cancer. This way, physicians have the possibility to recognize breast carcinoma in early stages. "At this point, the cancer can be treated way better than in later stages", says Mahdi Fallah, Group Leader of "Risk Adapted Prevention (RAD)" at DKFZ. "Many countries therefore initiated early detection programs". However, this has led to more women receiving the diagnosis of "breast cancer at an early stage", also called carcinoma "in situ" - which means there are pathologically-changed cells "in their normal place" in the mammary ducts, but these abnormal cells have not grown to surrounding tissue or metastasized, as is the case with progressed or invasive breast carcinoma.

Through increased detection of breast carcinoma in situ, more women consequently have such a case in their family. Up until now, it was unknown whether women with this family background are at higher risk of developing breast cancer. Such an association had only been shown for a family background with invasive carcinoma. "In these cases, we always recommend women to start early with screening examinations", says Elham Kharazmi, Co-Head of the study and scientist at the DKFZ, at the NCT and Statistical Genetics, Institute for Medical Biometry and Informatics at the University of Heidelberg. Existing guidelines also recommend regular and early prevention in case of the existence of this risk factor.

Fallah and his colleagues examined in the study at hand whether the risk of developing breast cancer also rises if there is a case of breast carcinoma in situ within the family. For their study, researchers used the nationwide Swedish family-cancer data sources - "the largest of their kind worldwide", says Fallah, Head of the study. Data come from pedigree register, which links families with descendants born after 1931 and their parents, as well as Swedish Cancer Registry data since 1958. Datasets are updated every two to three years. Overall, the Swedish data includes pedigree data of more than 12.8 million persons, around 1.7 million records of progressed cancers and about half a million of cases of early carcinoma.

During the study period, researchers investigated on data of more than five million women. At the end of the study, the large majority (87.6 percent) did not show a history of breast cancer in their first-degree and second-degree relatives. Of 40,352 women, whose female first-degree or second-degree relatives had breast carcinoma in situ, 584 developed invasive breast cancer during the follow-up period.

Women of all ages with first-degree relatives (mother, sister, or daughter) with breast carcinoma in situ had 1.5-fold risk of developing breast cancer over the life course - here always compared to women with no breast carcinoma cases in their family. If a first-degree relative had an invasive cancer, the risk was 1.7 times, for women under age 50 even twice as high. If a second-degree relative had breast carcinoma in situ, the risk grew by 1.2 times and by 1.3 times in case the cancer had been invasive.

In conclusion, even if the risk of developing cancer over the life course is a little bit higher for women with a family history of invasive cancer in comparison to women with carcinoma in situ, researchers did not find it significantly different. "The risk of developing breast cancer for women who have a family history of either carcinoma in situ or progressed carcinoma is quite similar", says Kharazmi and adds: "The results show that a family history of carcinoma in situ should not be ignored." She and her colleagues think that cancer prevention guidelines and recommendations for women with a family anamnesis of progressed breast carcinoma should also apply to women with a family anamnesis of breast cancer in early stages. Such a procedure could further improve the risk-adapted early detection of breast cancer.

Original publication
T. Mukama, M. Fallah, H. Brenner, X. Xu, K. Sundquist, J. Sundquist, and E. Kharazmi: Risk of invasive breast cancer in relatives of patients with breast carcinoma in situ: A prospective cohort study. BMC Medicine 2020, https://doi.org/10.1186/s12916-020-01772-x

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Press contact:

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German Cancer Research Center (DKFZ)
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National Center for Tumor Diseases (NCT) Heidelberg
The National Center for Tumor Diseases (NCT) Heidelberg is a joint institution of the German Cancer Research Center, Heidelberg University Hospital (UKHD) and German Cancer Aid. The NCT's goal is to link promising approaches from cancer research with patient care from diagnosis to treatment, aftercare and prevention. This is true for diagnosis and treatment, follow-up care or prevention. The interdisciplinary tumor outpatient clinic is the central element of the NCT. Here, the patients benefit from an individual treatment plan prepared in interdisciplinary expert rounds, so-called tumor boards. Participation in clinical studies provides access to innovative therapies. The NCT thereby acts as a pioneering platform that translates novel research results from the laboratory into clinical practice. The NCT cooperates with self-help groups and supports them in their work. Since 2015, the NCT Heidelberg has maintained a partner site in Dresden. The Hopp Children's Cancer Center (KiTZ) was established in Heidelberg in 2017. The pediatric oncologists at KiTZ work together in parallel structures with the NCT Heidelberg.

German Cancer Research Center (DKFZ)
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.
Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Cancer Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

Heidelberg University Hospital (UKHD)
Heidelberg University Hospital (UKHD) is one of the most important medical centers in Germany; Heidelberg University's Medical Faculty is one of Europe's most prestigious biomedical research facilities. Their shared objective is the development of innovative diagnostics and treatments and their prompt implementation for the benefit of the patient. The hospital and faculty employ approximately 13,000 individuals and are involved in training and qualification. Every year approximately 65,000 patients are treated as inpatients and 56,000 as day patients in more than 50 specialized clinical departments with around 2,000 beds, with more than 1 million patients being treated as outpatients. Together with the German Cancer Research Center and German Cancer Aid, the Heidelberg University Hospital established The National Center for Tumor Diseases (NCT) Heidelberg as the leading oncology center of excellence in Germany. The Heidelberg Curriculum Medicinale (HeiCuMed) is at the forefront of medical training in Germany. At present 3,700 aspiring physicians and doctors are studying in Heidelberg.