Per Hall

Per Hall

Professor/senior physician

About me

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. Part time 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 my three sons, one working, two still students.

Research description

Short presentation of current research

My overall and most important scientific goal is to contribute to lowering the incidence and mortality of breast cancer. Breast cancer is a potentially fatal disease that is increasing dramatically throughout the world. One woman a minute is diagnosed with breast cancer in Europe.

In order to do decrease incidence, we have to identify women at increased risk of breast cancer and to identify means to influence the risk. Such a risk prediction tool has to include detailed information on lifestyle factors, genetic markers and something called mammographic features. Several of my projects aim to identify these markers.

When we are able to identify women at high risk we will offer means to influence the risk as described in the Karisma study below.

The Karma project

The outcome of the Karma project is the prospective Karma Cohort. The Karma Cohort was established in close collaboration with four hospitals in Sweden, Södersjukhuset, Helsingborg, Landskrona and Lund. Women attending a mammography, screening or clinical, at any of these hospitals were invited to be part of the Karma Cohort from January 2011 to March 2013. Upon acceptance, participants filled out a web-based questionnaire and donate blood. Whole blood, plasma and DNA is stored at the Karolinska Institutet Biobank [https://ki.se/en/research/ki-biobank]. We also ask for informed consent to store the processed and raw mammograms and to link the personal ID to the Swedish Inpatient, Prescription, Cancer, Emigration/Immigration and Cause of Death Registers. Participants are also linked to the nationwide Breast Cancer Registry (INCA).

The Karma cohort is one of the best characterized breast cancer cohorts in the world and a unique resource for future studies of risk and prognosis of breast cancer [karmastudy.org]. An important aspect of the Karma project is that data are shared with researchers outside the group, department and country. We have built the Karma Research Platform that enables outside researchers to browse the content of Karma and request data. Several projects have been initiated ranging from quality of life to exosomes. The only prerequisite, besides ethics, is that results should be fed back in to the Karma Cohort when published, enabling the next generation of researchers to benefit from the data.

Publications

Cohort Profile: The Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA). Gabrielson M, Eriksson M, Hammarström M, Borgquist S, Leifland K, Czene K, et al Int J Epidemiol 2017 12;46(6):1740-1741g

Mammographic density

Mammographic density, the radiolucent part of the mammogram, consists of glandular and connective tissue. Mammographic density is a strong risk factor for breast and is influenced by age, BMI and hormone replacement therapy. The anti-hormonal therapy administrated to breast cancer patients post surgery decreases density. We have shown that a density decrease while on adjuvant tamoxifen is a strong prognosticator and influences breast cancer survival beyond 15 years of diagnosis.

Over the years we have developed a fully automated way of measuring the mammographic density, microcalcifications and so called masses. The tool forms the basis of the Karma risk model.

Publications

Mammographic density reduction is a prognostic marker of response to adjuvant tamoxifen therapy in postmenopausal patients with breast cancer. Li J, Humphreys K, Eriksson L, Edgren G, Czene K, Hall P J. Clin. Oncol. 2013 Jun;31(18):2249-56

A clinical model for identifying the short-term risk of breast cancer. Eriksson M, Czene K, Pawitan Y, Leifland K, Darabi H, Hall P Breast Cancer Res 2017 03;19(1):29

Risk modelling

We are working hard to develop a risk models that answers the question – who are the women sent home with a negative mammogram that will come back before or at next screen with a breast cancer? Using some few lifestyle factors, a polygenic risk score including 313 SNPs and a detailed analyses of mammographic features. We recently published a paper covering this topic. We have also initiated a collaboration with iCAD [https://www.icadmed.com] who have developed deep learning tools to automatically identify cancers on a mammogram.

Publications

Identification of Women at High Risk of Breast Cancer Who Need Supplemental Screening. Eriksson M, Czene K, Strand F, Zackrisson S, Lindholm P, Lång K, et al Radiology 2020 11;297(2):327-333

The Karisma project

The possible primary preventive measures for breast cancer ranges from increased physical activity to prophylactic mastectomy. However, lifestyle changes such as increased physical activity, weight loss and reduced intake of alcohol will only have minute influence on risk. Prophylactic removal of the breasts will dramatically lower the risk of breast cancer but at a high prize. An alternative would be risk-reducing medication, such as tamoxifen, where a number of studies have shown dramatic effects on breast cancer incidence. As an example, tamoxifen administrated to perfectly healthy women reduces the risk of breast cancer with ≈30%.

Starting 2016 and ending late 2019, 1,440 women aged 40-74 years and participating in the Swedish mammography screening program, were randomly assigned to placebo, 1, 2.5, 5 10 and 20 mg of tamoxifen. Outcomes were mammographic density change after 6 months exposure, and measures of safety and tolerability. In short, 2.5 mg of tamoxifen lowered mammographic density to the same extent as 20 mg but came with a 50% reduction in severe vaso-motor side effects.

Publications

Low dose tamoxifen for mammographic density reduction – a randomized controlled trial. Mikael Eriksson, Martin Eklund, Signe Borgquist, Roxanna Hellgren, Sara Margolin, Linda Thoren, Ann Rosendahl, Kristina Lång, José Tapia, Magnus Bäcklund, Andrea Discacciati, Alessio Crippa, Marike Gabrielson, Mattias Hammarström, Yvonne Wengström, Kamila Czene, Per Hall.

Radiation epidemiology

I am a professor of radiation epidemiology, with a focus on radiation associated late adverse health effects in women diagnosed with breast cancer. Recently, we managed to estimate the dose dependent risk of a myocardial infarction and identify particularly susceptible subgroups of women. This paper has had an enormous influence on how breast cancer patients are treated and has by far the highest citation rate of my papers.

Another important contribution was a paper published in 2004. We managed to show that low doses of ionizing radiation, equivalent to the dose of a CT scan of the skull, delivered in infancy influenced cognitive function in adult life. A finding that changed the way premature babies are handled.

Publications

Risk of ischemic heart disease in women after radiotherapy for breast cancer. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, et al N. Engl. J. Med. 2013 Mar;368(11):987-98

Effect of low doses of ionising radiation in infancy on cognitive function in adulthood: Swedish population based cohort study. Hall P, Adami HO, Trichopoulos D, Pedersen NL, Lagiou P, Ekbom A, et al BMJ 2004 Jan;328(7430):19

Research group

I conduct most of my projects in close collaboration with Professor Kamila Czene. Our group at the Department of Medical Epidemiology and Biostatistics consists of post docs and students, research nurses, data base managers, project leaders and administrative personnel. Most analyses are conducted in collaboration with statisticians at the department. We both have extensive and intense international collaboration.

Current main supervision of PhD students

Mattias Hammarström

Current co-supervision of PhD students

Roxanna Hellgren

Kejia Hu

Education

MD, PhD

Academic honours, awards and prizes

 

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