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Breast cancer liver metastases: incidence, prognosis and surgical treatment
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
2026 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Levermetastaser från bröstcancer : incidens, prognos och kirurgisk behandling (Swedish)
Abstract [en]

Despite great advances in the treatment of breast cancer, metastatic breast cancer is still a serious condition. The prognosis can differ significantly depending on which organs are affected. Liver metastases are associated with a poor prognosis. It is known that the properties of tumour cells change from the original tumour in the breast to the metastases, but this is incompletely described for liver metastases. Surgery of liver metastases has become a standard treatment for certain tumor diseases but is poorly studied in breast cancer. The aim of this thesis was to determine prognostic factors in breast cancer liver metastases and how tumour characteristics change from primary tumour to metastases. We also aimed to determine the incidence and timing of liver metastases. Finally the aim of the thesis was to evaluate how surgery of liver metastases affects survival and which factors control the results. All four included studies are retrospective registry studies. The results show that the properties of the tumour cells often change from primary breast cancer to liver metastases. Liver metastases are common in advanced breast cancer but isolated oligometastases (<5) are rare. Few patients have undergone surgery in Sweden due to liver metastases from breast cancer. In selected cases, surgery may be able to prolong survival.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2026. , p. 63
Keywords [en]
Breast cancer, Liver metastases, Surgery
National Category
Surgery
Identifiers
URN: urn:nbn:se:umu:diva-252506ISBN: 978-91-8070-990-3 (print)ISBN: 978-91-8070-991-0 (electronic)OAI: oai:DiVA.org:umu-252506DiVA, id: diva2:2055815
Public defence
2026-05-22, Aulan, Sunderby Sjukhus, Luleå, Sunderby Sjukhus, Sunderbyn, Luleå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2026-04-29 Created: 2026-04-27 Last updated: 2026-04-29Bibliographically approved
List of papers
1. Surgical treatment of breast cancer liver metastases: A nationwide registry-based case control study
Open this publication in new window or tab >>Surgical treatment of breast cancer liver metastases: A nationwide registry-based case control study
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2020 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 46, no 6, p. 1006-1012Article in journal (Refereed) Published
Abstract [en]

Introduction: The benefit of liver resection or ablation for breast cancer liver metastases (BCLM) remains unclear. The aim of the study was to determine survival after isolated BCLM in nationwide cohorts and compare surgical versus systemic treatment regimens.

Materials and methods: The Swedish register for cancer in the liver and the bile ducts (SweLiv) and the National register for breast cancer (NBCR) was studied to identify patients with 1-5 BCLM without extrahepatic spread diagnosed 2009-2016. Data from the registers were validated and completed by review of medical records. A Kaplan-Meier plot and log rank test were used to analyse survival. Prognostic and predictive factors were evaluated by Cox regression analysis.

Results: A surgical cohort (n = 29) was identified and compared to a control cohort (n = 33) receiving systemic treatment only. There was no 90-day mortality after surgery. Median survival from BCLM diagnosis was 77 months (95% CI 41-113) in the surgical cohort and 28 months (95% CI 13-43) in the control cohort, (p = 0.004). There was a longer disease-free interval and more oestrogen receptor positive tumours in the surgical cohort. Surgery was a significant positive predictive factor in univariate analysis while a multivariable analysis resulted in HR 0.478 (CI 0.193-1.181, p = 0.110) for surgical treatment.

Conclusion: Surgery for BCLM is safe and might provide a survival benefit in selected patients but prospective trials are warranted to avoid selection bias.

Place, publisher, year, edition, pages
Elsevier, 2020
Keywords
Breast cancer, Liver metastases, Liver resection, Liver ablation
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-172505 (URN)10.1016/j.ejso.2020.02.008 (DOI)000537625100011 ()32098734 (PubMedID)2-s2.0-85079894172 (Scopus ID)
Available from: 2020-07-02 Created: 2020-07-02 Last updated: 2026-04-27Bibliographically approved
2. Receptor conversion and survival in breast cancer liver metastases
Open this publication in new window or tab >>Receptor conversion and survival in breast cancer liver metastases
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2023 (English)In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 25, no 1, article id 105Article in journal (Refereed) Published
Abstract [en]

Background: Breast cancer liver metastases (BCLM) is a common cause of breast cancer-related death. The prognostic and predictive value of receptor expression and St Gallen classification is challenged by receptor status discordance in distant metastases. The aim of this study was to determine the rate of receptor conversion from breast cancer to BCLM and the impact on survival.

Method: Patients registered with BCLM in two Swedish national cancer registers were recruited retrospectively. Data on receptor expression in primary breast cancer and BCLM were collected, as well as information about predictive factors for survival. The rate of receptor and subtype conversion was analyzed. A Cox regression model was used to investigate predictive factors for survival.

Results: A cohort of 132 patients with BCLM was identified. Estrogen receptor (ER), progesterone receptor (PgR) and HER2 converted in 17, 33 and 10%, respectively. PgR was lost in BCLM while 8/10 HER2 conversions went from negative to positive. The BC subtype was re-classified in 21% of the BCLM. Median survival after BCLM was 13 months and HER2 amplification was associated with improved survival (HR 0.28 CI 0.085–0.90). The highest predictive value (Harrell´s C-index) was obtained when including both BC and BCLM status.

Conclusions: Receptor and subtype conversions are common in BCLM, and a liver biopsy is warranted to tailor BCLM treatment. HER2 amplification is associated with improved survival in a BCLM cohort.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
Breast cancer, Estrogen receptor, Human epidermal growth factor receptor 2, Liver metastases, Progesterone receptor
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-214618 (URN)10.1186/s13058-023-01706-4 (DOI)001075576500001 ()37705026 (PubMedID)2-s2.0-85171140754 (Scopus ID)
Funder
The Breast Cancer FoundationRegion VästerbottenNorrbotten County CouncilKnut and Alice Wallenberg FoundationSwedish Research Council
Available from: 2023-09-27 Created: 2023-09-27 Last updated: 2026-04-27Bibliographically approved
3. Impact of breast cancer characteristics on the development and time to liver metastases: population-based study
Open this publication in new window or tab >>Impact of breast cancer characteristics on the development and time to liver metastases: population-based study
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2026 (English)In: BJS Open, E-ISSN 2474-9842, Vol. 10, no 3, article id zrag036Article in journal (Refereed) Published
Abstract [en]

Background: Breast cancer (Bc) is the leading cause of cancer-related death in women. In many patients, BC liver metastases (BCLM) are associated with short survival. The aims of this study were to investigate the risk of and time to BCLM in each BC surrogate subtype, and to determine the incidence of BCLM in a population-based setting.

Methods: The Swedish national breast cancer registry identified patients with Bc in a regional cohort from 2009 to 2018. The cohort was followed until January 2023. Cox regression analysis was used to determine the risk of BCLM for each subtype. Kaplan–Meier estimates determined the probability of BCLM for each subtype over time.

Results: In all, 7292 patients with Bc were included in the study. Distant metastases developed in 755 patients (10.4%); of these, 345 (45.7%) developed BCLM. The BCLM incidence rate was 8 per 1000 person-years. Only 13 patients had oligometastases isolated to the liver. Triple-negative, non-luminal human epidermal growth factor receptor 2 (HER2)-positive and luminal B cancers had the highest risk of BCLM. T category, nodal status, and Nottingham histological grade III were also strongly associated with BCLM. The median time from Bc diagnosis to BCLM was 36 months. Patients with HER2-positive BC subtypes developed BCLM early, at a median of only 9 months.

Conclusion: Bc subtype is correlated to the risk and timing of BCLM development. BCLM are common in advanced Bc, but isolated oligometastases are rare.

Place, publisher, year, edition, pages
Oxford University Press, 2026
Keywords
Breast Surgery, Hepato-Pancreato-Biliary Surgery
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-252503 (URN)10.1093/bjsopen/zrag036 (DOI)001762651800001 ()42119146 (PubMedID)2-s2.0-105038618024 (Scopus ID)
Funder
Bröstcancerförbundet, 2018-0008Region Västerbotten, RV1014216
Available from: 2026-04-27 Created: 2026-04-27 Last updated: 2026-05-27Bibliographically approved
4. Breast cancer liver metastases and the impact of receptor expression on survival
Open this publication in new window or tab >>Breast cancer liver metastases and the impact of receptor expression on survival
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2026 (English)In: Clinical and Experimental Metastasis, ISSN 0262-0898, E-ISSN 1573-7276, Vol. 43, no 1, article id 8Article in journal (Refereed) Published
Abstract [en]

The aim was to determine the frequency of altered receptor expression between primary breast cancer and liver metastases, and to examine the impact of receptor expression on survival. The conversion frequency of estrogen- (ER), progesterone- (PgR) and human epidermal growth factor receptor 2 (HER2) was investigated. The prognostic value of the receptor status in the primary tumor versus the metastases was estimated. Data on a population-based regional cohort of 7292 breast cancer patients from 2009 to 2018 were collected from the National Breast Cancer Register. Biomarker expression and intrinsic subtype was studied among those who developed liver metastases with available histopathological records. The study included 311 patients with liver metastases. Conversion of ER, PgR and HER2 occurred in 16%, 47% and 12% of patients, respectively. The subtype converted in 26%. HER2 amplification in the primary tumor or metastases was associated with improved survival. Positive ER and PgR in breast cancer and positive ER in liver metastases were beneficial for survival. A combined primary tumor and metastasis receptor evaluation had the highest prognostic value. Receptor conversion from primary tumor to liver metastases is common. HER2 amplification and positive ER or PgR are associated with improved survival. Accordingly, luminal HER2 positive tumors have improved survival compared to other intrinsic subtypes. To personalize treatment for each patient, a liver biopsy is warranted at diagnosis of breast cancer liver metastases.

Place, publisher, year, edition, pages
Springer, 2026
Keywords
Breast cancer, Breast cancer liver metastases, Estrogen (ER), Human epidermal growth factor receptor 2 (HER2), Progesterone (PgR), Receptor conversion
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-248995 (URN)10.1007/s10585-025-10387-6 (DOI)001658828600001 ()41511682 (PubMedID)2-s2.0-105027120756 (Scopus ID)
Funder
Bröstcancerförbundet, 2018-0008Region Västerbotten, RV1014216
Available from: 2026-02-03 Created: 2026-02-03 Last updated: 2026-04-27Bibliographically approved

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