How likely are benign breast disease and premalignant lesions to progress to invasive breast cancer?
The aim is to add to what is known about the potential of personalized screening based on prior screening outcomes.
Status: Completed
The project used different types of data in order to increase our understanding of the risk of developing breast cancer among women who have experienced a false positive screening examination or have undergone treatment as a result of a screening-detected premalignant lesion in the breast.
Main findings: We investigated whether a number of negative (normal) screening results can be used to predict breast cancer risk for a woman who has participated in BreastScreen Norway. The results showed no association between the number of negative screening examinations and breast cancer risk among participating women. These results support the recommendation to all women in the target group of attending each screening invitation, regardless of how many times they have been screened with normal results in the past.
Analyzes of screening data for around 800,000 women with up to 21 years of follow-up showed an increased risk for women with a false positive screening examination or a premalignant lesion of later being diagnosed with breast cancer. The estimated risk increased with the assumed malignancy potential, from benign findings to the pre-cancerous lesion DCIS. We found no difference in how the tumor characteristics of subsequent breast cancer cases were statistically distributed within the groups, with the exception of a lower proportion of positive lymph node status among those with invasive breast cancer after in situ carcinoma. The authors concluded that women with benign lesions or hyperplasia with atypia may benefit from being screened more frequently than every other year. The costs of an adapted screening scheme like this must be investigated.
Analyzes of women's self-reported lifestyle, using information from a questionnaire used in BreastScreen Norway 2006-2015, showed an increased risk of developing breast cancer among women who used HRT and had a biopsy with a benign or negative result. Beyond this, the study could neither confirm nor refute whether modifiable risk factors for breast cancer, including alcohol intake, smoking habits and little physical activity, were associated with increased breast cancer risk among women who have experienced a false positive screening test or detection of a premalignant lesion.
Based on data from a national review study, in which screening mammograms showing DCIS were re-evaluated by radiologists, the research group compared standardized radiological descriptions of calcifications on mammograms for women who later developed and did not develop invasive breast cancer. The main finding was that "fine linear branching" was associated with an increased risk of later developing invasive breast cancer. It is previously known that tumours with this calcification pattern are associated with worse prognosis than tumours with other calcification patterns.
Background
BreastScreen Norway is a public health service, and invites all women in Norway between 50 and 69 years to have a screening mammogram (x-ray image of the breast) every other year.
On most of the attending women's mammograms, there are no findings, and we say that these women are screened negative. Actually, only 3% of women attending BreastScreen Norway have uncertain or suspicious findings on their mammograms. These women are recalled for additional assessment. Among women recalled, three out of five are evaluated negative (healthy) after additional imaging, without any additional tests. A needle biopsy is required for the remaining two out of five recalled women.
This means that a small group of women is selected for a needle biopsy. About half of these women have breast cancer or a precursor requiring treatment. The other half shows a wide spectrum of benign results, from normal cells via atypical cell changes to in situ lesions. In situ lesions are cells that have initiated a possible development towards breast cancer, but where the changes are located only within the milk ducts or breast lobule.
Purpose
This postdoctor project is part of a larger project where researchers from different disciplines are working together to add to what is known about benign findings in the breast and precursors of breast cancer. The project may contribute in identifying the optimal follow-up for women with different types of findings from prior screening(s), and may increase our knowledge about the process where normal cells develop into breast cancer. The project may also contribute to increased knowledge about overdiagnosis and overtreatment of breast cancer.
All women recalled for additional imaging in BreastScreen Norway have in common that something on their mammograms prompted the radiologists to have a second look. We know from previous studies that this group of women has an increased long term risk of breast cancer. The first step of this project was to make more systematic and precise estimates of the risk of progression for different types of benign findings and precursors to breast cancer. The second step is to investigate how the risk of progression depends on epidemiological risk factors among women with prior mammographic findings.
We, and many other researchers worldwide, show special interest for the precursors of breast cancer where cells have initiated a progression towards breast cancer within the milk ducts, Ductal Carcinoma In Situ (DCIS). Today, all Norwegian women diagnosed with DCIS are treated surgically, often also with radiation treatment, due to their increased risk of developing breast cancer if left untreated. Researchers in the US, Great Britain, Belgium and the Netherlands are currently running ground-breaking studies of watchful waiting in order to identify subgroups of women with this diagnosis who may not need treatment. This could be the case for DCIS lesions where the cell changes only to a small degree are similar to the changes seen in invasive breast cancer. As part of our project, we are organizing a radiological review where radiologists are evaluating selected characteristics of screening mammograms showing DCIS. The aim of our subsequent analysis is to identify mammographic features predicting higher or lower risk of developing invasive breast cancer.
Planned studies and status
Study 1: Estimate the risk of developing invasive breast cancer among Norwegian women with prior benign breast disease or a premalignant lesion, for different types of lesions and compared to women who are screened negative.
Published:
Number of prior negative screening outcomes does not influence future risk of breast cancer. Lilleborge M. et al, Eur J Epidemiol. 2020 Jun;35(6):549-556.
Risk of breast cancer by prior screening results among women participating in BreastScreen Norway. Lilleborge M. et al, Cancer. 2019 Oct 1.
Study 2: Identify epidemiological risk factors of progression to invasive breast cancer among women with prior benign breast disease or premalignant lesion. Published: Can breast cancer be stopped? Modifiable risk factors of breast cancer among women with a prior benign or premalignant lesion. Lilleborge M. et al, Int J Cancer 2021, May 14
Study 3: Identify mammographic features on initial screening mammograms showing DCIS which predict an increased [or decreased] risk of progression to invasive breast cancer. Published: Patterns of aggressiveness: risk of progression to invasive breast cancer by mammographic features of calcifications in screen-detected ductal carcinoma in situ. Lilleborge M. et al, Acta Radiolol 2021, Apr 22.
Research team
The project is carried out by Marie Lilleborge (PhD) and section for breast cancer screeening at the Cancer Registry of Norway.
Mentors and supervisors of this project are Solveig Hofvind, head of section for breast cancer screening in the Cancer Registry of Norway and Professor of radiography at Oslo Metropolitan University, and Giske Ursin, Director of the Cancer Registry of Norway.
External collaborators include:
- Ragnhild Sørum Falk, Oslo University Hospital
- Therese Sørlie, Oslo University Hospital
- Hege Russnes, Oslo University Hospital
- Torill Sauer, Akershus University Hospital
- Marit Muri Holmen, Oslo University Hospital
- Tone Bøe Aaman Vamre, Oslo University Hospital
- Elisabete Weiderpass, International Agency for Research on Cancer (IARC)
- Ellen Schlichting, Oslo University Hospital
- Vessela Kristensen, Oslo University Hospital
- Anne-Lise Børresen-Dale, Oslo University Hospital
- Gry Geitvik, Oslo University Hospital
- Åslaug Helland, Oslo University Hospital
- Vilde Drageset Haakensen, Oslo University Hospital
