Per Hall

After graduation at the University of Lund I started working as a medical oncologist at Department of Oncology, Karolinska Hospital, in 1984. During my sixteen years at Radiumhemmet I initiated and headed the Hereditary Breast Cancer Unit and later the Cancer Epidemiology Unit. I defended my thesis in the field of Radiation Epidemiology in 1991. 

I started working as a full time epidemiologist at the Department of Medical Epidemiology and Biostatistics in 2000. Today my research focus is breast cancer prevention and early detection. I have moved back to clinical practice with a focus on clinical research as I have a part time position at Södersjukhuset, Stockholm.

Since 1996 I have coordinated six European Commission and two NIH projects. Besides the ordinary national funding agencies, I have received funding from private donations and the Stockholm County Council.

My strength as a researcher is that questions asked and hypothesis generated are all based in my clinical background. I want my results to have clinical implications.

However, research is not the most important part of life, that’s golf, friends and family, in reversed order. 

Current Research Overview

My primary scientific goal is to contribute to reducing the incidence and mortality of breast cancer. This potentially fatal disease is on the rise worldwide, with one woman diagnosed every minute in Europe—corresponding to one in eight women diagnosed during their lifetime.

To decrease breast cancer incidence, we must identify women at increased risk and explore ways to influence that risk. A comprehensive risk prediction tool should incorporate detailed lifestyle factors, genetic markers, and mammographic features. Several of my projects focus on identifying these key markers. Once we identify high-risk women, we should offer strategies to modify their risk and improve early detection.

The Karma Project

The first sub-project of the Karma initiative involved establishing the Karma Screening Cohort in collaboration with four hospitals in Sweden [doi: 10.1093/ije/dyw357]. From January 2011 to March 2013, women attending either screening or clinical mammography at these hospitals were invited to join the Karma Cohort. The approximately 70, 000 participants completed a web-based questionnaire and donated blood. We store whole blood, plasma, and DNA at the Karolinska Institutet Biobank [https://ki.se/en/research/ki-biobank], with informed consent obtained for storing processed and raw mammograms and linking personal IDs to Swedish health registers, including the nationwide Breast Cancer Registry (INCA).

The Karma Cohort is among the best-characterized breast cancer cohorts globally, serving as a unique resource for studying risk and prognosis [karmastudy.org]. A key aspect of the Karma project is our commitment to data sharing with researchers outside our group, department, and country. The Karma Research Platform allows external researchers to browse the dataset and request data. Several projects have emerged, ranging from quality of life studies to exosome research, with the stipulation that published results be fed back into the Karma Cohort for the benefit of future researchers.

Mammographic Density

Mammographic density, the radiolucent part of a mammogram, consists of glandular and connective tissue and is a strong risk factor for breast cancer. Mammographic density is influenced by age, BMI, hormone replacement therapy and most factors that influences the risk of breast cancer. Anti-hormonal therapy post-surgery, such as tamoxifen, decreases density. We have shown that a reduction in density while on adjuvant tamoxifen is a strong prognostic indicator, influencing breast cancer survival beyond 15 years [doi: 10.1200/JCO.2012.44.0906].

We have developed a fully automated system for measuring mammographic density, microcalcifications, focal masses, and density changes over time, forming the basis of the Karma risk model [doi: 10.1007/s10549-018-4690-5].

Risk Modelling

We are focused on developing a risk model that addresses the question: Who are the women sent home with a negative mammogram but will return with breast cancer before or at their next screening? By analysing a limited number of lifestyle factors, a polygenic risk score comprising 313 SNPs, and detailed mammographic features, we can identify women at increased risk of interval cancer [doi: 10.1126/scitranslmed.abn3971]. We have also initiated a collaboration with iCAD, which has developed deep learning tools for automatic cancer detection in mammograms [https://www.icadmed.com].

The Karisma Project

Preventive measures for breast cancer range from increased physical activity to prophylactic mastectomy. While lifestyle changes can only minimally influence risk, prophylactic mastectomy significantly reduces breast cancer risk but carries substantial costs. An alternative is risk-reducing medication, such as tamoxifen, which has shown a dramatic effect on breast cancer incidence. Tamoxifen has been shown to reduce breast cancer risk by approximately 30% in healthy women.

From 2016 to late 2019, 1, 440 women aged 40-74 participating in the Swedish mammography screening program were randomly assigned to placebo or varying doses of tamoxifen (1, 2.5, 5, 10, and 20 mg). The primary outcomes included changes in mammographic density after six months and assessments of safety and tolerability. Notably, 2.5 mg of tamoxifen produced the same decrease in mammographic density as 20 mg, with a 50% reduction in severe vasomotor side effects [doi: 10.1200/JCO.20.02598].

Tamoxifen is metabolized into approximately 20 metabolites in the liver, with endoxifen theorized to be primarily responsible for its effects, though not for all side effects. We launched a placebo-controlled, randomized, three-armed, double-blinded study, concluding recruitment in summer 2024, with results expected by late 2024.

SMART

SMART (Stockholm Mammography Risk Stratified Trial) will include 70, 000 women, half of whom will receive risk-stratified screening. Women in the intervention group will undergo risk assessment, with high-risk individuals offered contrast-enhanced mammography. The primary outcome is the frequency of interval cancers in both arms. This project commenced in spring 2024 and is sponsored by Atossa Therapeutics [https://atossatherapeutics.com].

Radiation Epidemiology

As a professor of radiation epidemiology, I focus on late adverse health effects in women diagnosed with breast cancer due to radiation exposure. In a European Commission-funded project, we estimated the dose-dependent risk of myocardial infarction in breast cancer patients receiving post-operative radiotherapy [doi: 10.1056/NEJMoa1209825]. We also identified particularly susceptible women, significantly impacting breast cancer treatment practices and achieving the highest citation rate among my publications.

Another key contribution was a 2004 paper demonstrating that low doses of ionizing radiation, equivalent to a CT scan of the skull, delivered in infancy can affect cognitive function in adulthood [doi: 10.1136/bmj.328.7430.19], influencing how premature infants are treated.

Supervision to doctoral degree

• Johanna Holm, Aggressive breast cancer: epidemiological studies addressing disease heterogeneity, 2023
• Roxanna Hellgren, Beyond mammography: an evaluation of complementary modalities in breast imaging, 2023
• Kejia Hu, Psychological distress and breast cancer: a bidirectional link, 2022
• Rickard Strandberg, Breast cancer natural history models and risk prediction in mammography screening cohorts, 2022
• Mattias Hammarström, Investigating the outcome of low and standard dose tamoxifen in healthy women, 2021-
• Mikael Eriksson, Risk assessment and prevention of breast cancer, 2021
• Shadi Azam, Determinants and influence of mammographic features on breast cancer risk, 2020
• Emilio Ugalde Morales, Molecular epidemiology studies on risk factors for breast cancer and disease aggressiveness, 2020
• Haomin Yang, Panorama of diseases associated with breast cancer, 2018
• Linda Abrahamsson, Statistical models of breast cancer tumour progression for mammography screening data, 2018
• Fredrik Strand, Determinants of interval cancer and tumor size among breast cancer screening participants, 2016
• Tang Trinh, Determinants of breast cancer risk: focusing on mammographic density, 2016
• Edoardo Colzani, Health outcomes of women with breast cancer, 2014
• Hatef Darabi, Genetic association and risk prediction of breast cancer from an epidemiological and biostatistical perspective, 2012
• Maria Sandberg (Schelin), Contralateral Breast Cancer - Risk and Prognosis, 2012
• Louise Eriksson, Mammographic density and breast cancer phenotypes, 2012
• Jingmei Li, Genetic determinants of breast cancer risk, 2011
• Chantal Mascarenhas (Orgéas), Endogenous and exogenous hormonal factors in female cancers – studies of risk and prognosis, 2009
• Mikael Hartman, Risk and prognosis of breast cancer among women at high risk of the disease, 2007
• Kristjana Einarsdottir, Genetic determinants of postmenopausal breast and endometrial cancer, 2007
• Michaela Prochazka, The risk of second primary lung carcinoma in breast cancer patients, 2006
• Catharina Ihre Lundgren, Incidence and prognosis of differentiated thyroid cancer in Sweden, 2006
• Lena Rosenberg, Hormone-related factors and breast cancer: studies of risk and prognosis, 2006
• Ullakarin Nyberg, Mortality and cancer incidence following cerebral angiography with thorotrast, 2002
• Kjell Bergfeldt, 2001