Breast cancer is genetically and histologically heterogenous, and is influenced by a variety of factors, including the tumor microenvironment (TME). The PAM50 subtypes; Luminal A, Luminal B, Normal-like, Basal-like and Her2-enriched, are associated with different tumor phenotypes and overall survival. The quantity and quality of immune cell infiltration in breast tumors play a key role in cancer development and progression and are associated with survival and treatment response. We used multiplex immunohistochemistry, single-cell RNA sequencing, and two deconvolution algorithms to explore the immune landscape across PAM50 subtypes. Immunostaining of CD3+ T cells, tryptase+ mast cells, CD20+ B cells, CD68+ CD163+ macrophages, and CD66b+ granulocytes revealed marked differences in tumor immune infiltrates according to breast cancer subtypes. Luminal tumors were relatively deprived of T cells and B cells, while exhibiting sparse to moderate amounts of macrophage infiltration. In contrast, Her2-enriched tumors exhibited a moderate immune presence, with sparse to moderate T cell infiltration and moderate infiltration of B cells and macrophages. At the other end of the spectrum, Basal-like tumors stood out for their strikingly rich immune environment and are heavily infiltrated by T cells, B cells, and macrophages. The results from the single-cell and deconvolution analyses confirmed subtype-specific immune microenvironments, which also allowed us to observe increased levels of natural killer (NK) and CD8+ T cells in Her2-enriched and Basal-like subtypes. In conclusion, our findings demonstrate significant differences in the immune tumor microenvironment between the established breast cancer molecular subtypes.

Background Invasive lobular carcinoma (ILC) has distinct features, including E-cadherin loss, single-file growth, frequent multifocality, complicating imaging and surgical planning. Treatment strategies often mirror those for invasive carcinoma of no special type. We evaluated the association between planned and final surgery, primary surgery (PS) vs neoadjuvant systemic therapy (NST), focusing on breast conserving treatment (BCT) rates, and treatment responses in ILC. Methods We performed a retrospective analysis of 104 biopsy-proven ILC cases diagnosed in 2018. Cases were stratified by treatment scheme: NST (n = 51) or PS (n = 53). Primary endpoints were definitive surgical procedure, resection margin status, treatment response (radiologic and pathological), and axillary downstaging. Secondary analyses assessed concordance between preoperative imaging and final pathological tumor size. Results Overall, 70% underwent mastectomy. In the NST group, only 33% (3/9) of cases initially planned for BCT achieved margin-negative BCT, resulting in lower observed BCT rates compared with PS. Positive margins were identified in 8.4% of cases, equally distributed between groups. In the NST group, 56.9% demonstrated pathological tumor size reduction, while 43.1% showed no objective response. In ER+/HER2- tumors, chemotherapy-based regimens did not improve response compared with endocrine-based therapy. Pathological complete response (pCR) was achieved exclusively in HER2 + disease (3/3). Axillary pCR was observed in 7.1% of clinically node-positive cases. Conclusions In this ILC cohort, BCT rates were low. NST was associated with a limited pathological response and infrequent conversion to BCT. Within this ILC cohort, surgical de-escalation was infrequent; whether this pattern reflects ILC-specific biology or shared institutional practice patterns awaits validation against a contemporaneous internal IC-NST comparator.

Background: Breast cancer is a heterogeneous disease with many drivers involved I disease progression. Diagnosis and treatment decisions are guided by clinical, pathological, and molecular markers. The PAM50 subtypes which include Luminal A, Luminal B, Normal-like, Basal-like and HER2-enriched, are associated with different tumour phenotypes and overall survival. In breast cancer, immune infiltration influences treatment response and disease outcome. In estrogen receptor negative and basal-like breast cancers a higher degree of immune cell infiltration has been associated with improved survival and enhanced responses to treatment. The recruitment of different immune cell types has different effect on the tumor growth and sensitivity to treatment Understanding the function and phenotypes of immune cell types in breast tumors may allow to better map which immune cell types may explain subtype specific tumor pathogenesis. Aim and method: Using two deconvolution algorithms, CIBERSORT and xCell, we aim at investigating whether the PAM50 subtypes have different immune microenvironment landscapes. We used 15 independent publicly available breast cancer cohorts with transcriptomics available for which, we inferred tumor immune cell infiltration. To experimentally assess the association between breast cancer subtypes and immune microenvironment, stained was performed on 80 tumors spanning the PAM50 subtypes for marker genes defining 6 minor immune cell types. Results: Unsupervised clustering of the CIBERSORT scores inferring for the quantity of 22 immune cell types in the tumor and xCell scores predicting for the presence of 64 cell types showed that the immune microenvironment was strongly correlated with the molecular PAM50 subtypes. We also found differences in the immune microenvironment of Luminal A and B subtypes, which are considered close in lineage, with the Luminal A subtype showing higher infiltration of mast cells while and Luminal B‘s higher infiltration of regulatory T cells. The HER2-enriched exhibits a microenvironment with high amount of plasma cells and neutrophils. Finally, Basal-like tumors have in general higher immune infiltration characterized by of natural killer cells, cytotoxic T cells and dendritic cells. Conclusion: Our findings show that the PAM50 subtypes may have overall differences in their immune microenvironment landscape which could be taken in consideration when explaining response to therapy or prognosis. Citation Format: Lilly Anne Torland, Jürgen Geisler, Youness Azimzade, Linn Buer, Jon Lømo, Øystein Garred, Inger Øynebråten, Astri Frafjord, Alexandre Benoit Corthay, Andliena Tahiri, Marianne Lyngra, Kristine Sahlberg, Vessela Kristensen, Xavier Tekpli. Assessment of the immune microenvironment of the breast cancer PAM50 Subtypes – a deconvolution approach [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-06-28.

BACKGROUND:Gene expression profiling tests such as the Prosigna-assay are used to aid adjuvant treatment decisions in hormone receptor positive (HR+) HER2 negative (HER2-) early breast cancer (EBC). In this evaluation, the cost-effectiveness of Prosigna against immunohistochemical (IHC) markers including Ki-67, was evaluated from the Norwegian healthcare- and societal perspective. MATERIALS AND METHODS:The treatment decision impact of Prosigna was tested in the prospective, observational EMIT-1 trial. Using individual data collected the first 12 months post-surgery, a decision model was built to project the economic consequences of using the Prosigna compared to IHC-markers for the adjuvant treatment decisions. Health benefits were measured by cost per quality-adjusted life-years (QALYs) and data on income and welfare benefit was obtained from Statistics Norway. RESULTS:Of 2,178 HR+/HER2- pN0 EBC patients in the EMIT-1 trial, 1,985 had available health economic data and 1,850 had complete income and welfare benefit records. Including all pN0 patients in the Prosigna-test strategy, the test was above the cost-effective threshold (€26,000; incremental cost-per QALY gained (ICER) €255,622) in a healthcare sector perspective. Incorporating also productivity costs, Prosigna was cost-saving (ICER €-435,677). Restricting Prosigna-testing to patients assessed as clear/uncertain chemotherapy candidates, the strategy was cost-effective in both the healthcare and societal perspective (ICER €8884 and €-620170, respectively). CONCLUSIONS:Using the Prosigna-assay for all HR+/HER2- pN0 EBC patients was not cost-effective from a healthcare perspective, but from the societal perspective it was cost-saving. Selecting patients who are clear/uncertain candidates for chemotherapy based on IHC-classification, Prosigna is cost-effective from both perspectives.

BACKGROUND:At diagnosis, 30-40% of women with breast cancer have metastases in sentinel (SN) or axillary lymph nodes (ALN). Nodal status is a strong prognostic factor and guides treatment decisions. Immune checkpoint inhibition has shown some efficacy, which can increase in the neoadjuvant setting. A better understanding of how tumour cells in primary tumours and metastatic lymph nodes shape the local immune microenvironment may provide clues for more individualized therapeutic interventions. METHODS:We conducted deep immunophenotypic analysis of 29 primary breast tumours and 36 lymph nodes from 38 patients with primary operable breast cancer. RESULTS:The immune profile of the primary tumour was not predictive of the lymph node immune profile or metastatic status. Primary tumours showed prominent CD8 T cell exhaustion and activated regulatory T cells, and the frequencies of these subsets were associated with tumour size. The immune cell profile in lymph nodes were different from the profile in primary tumours, except for the ALN+ nodes, which displayed a T-cell profile more similar to primary tumours. The frequencies of the T cell subsets in lymph nodeswere associated with metastatic size. Tumour cells from smaller metastases exhibited a distinct phenotype compared to those from larger tumour deposits, and the size of the tumour cell deposit impacted the local immune cell composition. CONCLUSION:The tumour size of primary tumours and metastatic size in lymph nodes are the main drivers of changes in immune cell composition.

Background Tumor immune cell infiltration is a favorable prognostic factor in triple-negative breast cancer. Most triple-negative tumors belong to the aggressive basal-like subtype. We hypothesized that immune gene expression may identify low-risk patients for whom adjuvant chemotherapy can be de-escalated. Methods The expression of 753 immune-related genes was analyzed in tumor biopsies from 45 patients with basal-like disease and no lymph node metastases (Oslo1 cohort) and evaluated for prognostic value. Findings were validated in two independent cohorts. Oslo1 biopsies were also analyzed for tumor-infiltrating lymphocytes (TIL) and tertiary lymphoid structures (TLS). Results Here we show that a high expression of CTLA4 (above 63 rd percentile) is associated with an excellent prognosis in the Oslo1 cohort. None of the patients in the CTLA4 high group suffered disease recurrence (median follow-up 7.4 years) or breast cancer-related death (median follow-up 17.7 years). Analysis of the SCAN-B (n = 233; 97% without distant recurrence in CTLA4 high group) and METABRIC cohorts (n = 155; 93% disease-specific survival in CTLA4 high group) validates this finding, which also applies to patients who did not receive chemotherapy. CTLA4 expression correlates with TIL score and TLS levels (Oslo1 cohort), but no TIL low / CTLA4 high patients died from breast cancer, suggesting that the CTLA4 readout identifies low-risk patients not captured by TIL assessment. Conclusions A high primary tumor expression of CTLA4 identifies patients with an excellent prognosis, for whom standard chemotherapy may be de-escalated or omitted.

BackgroundEMIT-1 is a national, observational, single-arm trial designed to assess the value of the Prosigna, Prediction Analysis of Microarray using the 50 gene classifier (PAM50)/Risk of Recurrence (ROR), test as a routine diagnostic tool, examining its impact on adjuvant treatment decisions, clinical outcomes, side-effects and cost-effectiveness. Here we present the impact on treatment decisions.Patients and methodsPatients with hormone receptor-positive, human epidermal growth factor receptor 2-negative pT1-pT2 lymph node-negative early breast cancer (EBC) were included. The Prosigna test and standard histopathology assessments were carried out. Clinicians’ treatment decisions were recorded before (pre-Prosigna) and after (post-Prosigna) the Prosigna test results were disclosed.ResultsOf 2217 patients included, 2178 had conclusive Prosigna results. The pre-Prosigna treatment decisions were: no systemic treatment (NT) in 27% of patients, endocrine treatment alone (ET) in 38% and chemotherapy (CT) followed by ET (CT + ET) in 35%. Post-Prosigna treatment decisions were 25% NT, 51% ET and 24% CT + ET, respectively. Adjuvant treatment changed in 28% of patients, including 21% change in CT use. Among patients assigned to CT + ET pre-Prosigna, 45% were de-escalated to ET post-Prosigna. Of patients assigned to ET, 12% were escalated to CT + ET and 8% were de-escalated to NT; of those assigned to NT, 18% were escalated to ET/CT + ET. CT was more frequently recommended for patients aged ≤50 years. In the subgroup with pT1c-pT2 G2 and intermediate Ki67 (0.5-1.5× local laboratory median Ki67 score), the pre-Prosigna CT treatment decision varied widely across hospitals (3%-51%). Post-Prosigna, the variability of CT use was markedly reduced (8%-24%). The correlation between Ki67 and ROR score within this subgroup was poor (r = 0.25-0.39). The median ROR score increased by increasing histological grade, but the ROR score ranges were wide (for G1 0-79, G2 0-90, G3 16-94).ConclusionThe Prosigna test result changed adjuvant treatment decisions in all EBC clinical risk groups, markedly decreased the CT use for patients categorized as higher clinical risk pre-Prosigna and reduced treatment decision discrepancies between hospitals.

Immune checkpoint inhibitors (ICIs) have been introduced in breast cancer (BC) treatment and better biomarkers are needed to predict benefit. Circulating tumor cells (CTCs) are prognostic in BC, but knowledge is limited on CTCs in the context of ICI therapy. In this study, serial sampling of CTCs (CellSearch system) was evaluated in 82 patients with metastatic BC enrolled in two randomized trials investigating ICI plus chemotherapy. Programmed death‐ligand 1 (PD‐L1) expression on CTCs was also measured. Patients with ≥ 2 CTCs per 7.5 mL at baseline had gene expression profiles in tumor suggestive of increased T‐cell activity, including increased tumor inflammation signature (TIS) in both triple‐negative (P = 0.010) and hormone receptor‐positive (P = 0.024) disease. Patients with luminal A BC had higher CTC levels. The association between CTC status and outcome was most apparent 4 weeks into therapy. PD‐L1 expression in CTCs was observed in 6/17 CTC‐positive patients and was associated with inferior survival. In conclusion, our study indicates that CTC numbers may inform on tumor immune composition, as well as prognosis. These findings suggest a potential of using CTCs as an accessible biomarker source in BC patients treated with immunotherapy.

Background: Immune checkpoint inhibitors (CPI) have shown efficacy against metastatic triple negative breast cancer (mTNBC), but only for PD-L1 positive tumors. It is not known if so-called immunogenic chemotherapies may yield clinical relevant synergies with CPI. We addressed these issues, by conducting a trial evaluating atezolizumab (anti-PD-L1) in combination with doxorubicin, which has been reported to provoke immunogenic cell death, and low-dose metronomic cyclophosphamide, which has been reported to counter immunosuppressive cells. The pegylated liposomal form of doxorubicin (PLD) was selected to avoid steroids and allow for long term therapy in responders. To our knowledge, this is the first randomized trial reporting on the concomitant addition of CPI to antracyclines in mTNBC. Methods: The trial enrolled patients with mTNBC and maximum one previous line of chemotherapy in the metastatic setting. Patients were randomized 2:3 into arm A (n=28), receiving chemotherapy alone, or arm B (n=40), receiving chemotherapy in combination with atezolizumab (840 mg every 2nd week). The chemotherapy consisted of PLD (20mg/m2 every 2nd week) + oral cyclophosphamide (cyclo; 50mg/day, 2/4 weeks) in both arms. The per protocol (PP) population was defined as patients receiving > 3 doses of atezolizumab and >2 doses of PLD. The primary efficacy endpoint was progression-free survival (PFS) in the PP population. The protocol power analysis focused on durable response, as measured by 15 months PFS. Safety, a co-primary endpoint, was evaluated in all patients that started therapy (Full Analysis Set; FAS). Secondary endpoints included PFS in FAS, objective response rate (ORR), clinical benefit rate (CBR), durable response rate (>6 months; DRR), overall survival (OS) and biomarkers. PD-L1 status was determined retrospectively by the Ventana SP142 assay, as tumor-infiltrating immune cells with cut-off ≥ 1%. Efficacy data are given in the PP population unless stated otherwise. Hazard ratios (HR) are given with 95% confidence intervals (CI). Results: A total of 68 patients started therapy (FAS), of which 59 were in the PP population and 57% had not received previous chemotherapy in the metastatic setting. PFS was significantly improved in arm B compared to arm A in both the PP population (HR 0.57; CI 0.33-0.99; p=0.0477) and in the FAS (HR 0.56; CI 0.33-0.95; p=0.0326). Median PFS was 4.3 months in arm B versus 3.5 months in arm A. The progression-free proportion after 15 months was 14.7% (CI 6.4-30.1%) in arm B versus 0% in arm A. The ORR was 30.6%/21.7%, CBR was 52.8%/43.5% and DRR was 13.9%/4.3% in arm B/A. The PFS advantage was observed for both PD-L1+ (n=27; HR 0.58) and PD-L1- subjects (n=31; HR 0.66). All five patients without progression after 15 months belonged to arm B, and three out of these patients were PD-L1 negative. Serious adverse events occurred for 48% in arm B and 29% in arm A (FAS). The most common immune related adverse events of any grade in arm B/A were hypothyroidism (10.0%/7.1 %), pneumonitis (10.0%/3.6%), hyperthyroidism (5.0%/7.1%) and rash (7.5%/3.6%). Further biomarker analyses and assessments of immunological changes during therapy are ongoing. Conclusions: The addition of atezolizumab to PLD and low-dose metronomic cyclophosphamide significantly improved PFS. A benefit was indicated also in patients with PD-L1 negative disease. The combination regimen was well tolerated with no new safety signals. Results from the ongoing analyses of consecutive tumor and blood samples will be important to assess the hypothesized immunological effects of the chemotherapy and to investigate biomarkers associated with the response to the combined treatment. Citation Format: Jon Amund Kyte, Andreas H. Røssevold, Nikolai K. Andresen, Christina Annette Bjerre, Bjørnar Gilje, Erik Hugger Jakobsen, Sunil Xavier Raj, Ragnhild Sørum Falk, Elin Borgen, Thea Jahr, Øystein Garred, Jon Lømo, Randi Margit Mathiesen, Bjørn Naume. PD11-11 Results from ALICE – Atezolizumab Combined with Immunogenic Chemotherapy in Patients with Metastatic Triple Negative Breast Cancer, a Randomized Phase IIb Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD11-11.

Immune checkpoint inhibitors have shown efficacy against metastatic triple-negative breast cancer (mTNBC) but only for PD-L1 positive disease. The randomized, placebo-controlled ALICE trial ( NCT03164993 ) evaluated the addition of atezolizumab (anti-PD-L1) to immune-stimulating chemotherapy in mTNBC. Patients received pegylated liposomal doxorubicin (PLD) and low-dose cyclophosphamide in combination with atezolizumab (atezo-chemo; n = 40) or placebo (placebo-chemo; n = 28). Primary endpoints were descriptive assessment of progression-free survival in the per-protocol population (>3 atezolizumab and >2 PLD doses; n = 59) and safety in the full analysis set (FAS; all patients starting therapy; n = 68). Adverse events leading to drug discontinuation occurred in 18% of patients in the atezo-chemo arm (7/40) and in 7% of patients in the placebo-chemo arm (2/28). Improvement in progression-free survival was indicated in the atezo-chemo arm in the per-protocol population (median 4.3 months versus 3.5 months; hazard ratio (HR) = 0.57; 95% confidence interval (CI) 0.33–0.99; log-rank P = 0.047) and in the FAS (HR = 0.56; 95% CI 0.33–0.95; P = 0.033). A numerical advantage was observed for both the PD-L1 positive ( n = 27; HR = 0.65; 95% CI 0.27–1.54) and PD-L1 negative subgroups ( n = 31; HR = 0.57, 95% CI 0.27–1.21). The progression-free proportion after 15 months was 14.7% (5/34; 95% CI 6.4–30.1%) in the atezo-chemo arm versus 0% in the placebo-chemo arm. The addition of atezolizumab to PLD/cyclophosphamide was tolerable with an indication of clinical benefit, and the findings warrant further investigation of PD1/PD-L1 blockers in combination with immunomodulatory chemotherapy.

Purpose There are several reasons to report days as being unusual with regard to dietary intake, including special occasions and celebrations. For breast cancer patients during the 12 month post-surgery period, unusual days may also include days that are affected by being a cancer patient. The aim of this study was to study dietary intake on “normal” and “unusual” days, and to study what is reported in “free text fields” of a food diary. Methods Women ( n = 456), mean age 55.5 years newly diagnosed with invasive breast cancer (stage I/II) were included in this clinical study. “Normal” and “unusual” days in general, over time and during the week and weekends were studied using repeated administration of a 7-day pre-coded food diary. Results The breast cancer patients reported 26% of all days as unusual. The intake of energy, most nutrients, especially alcohol and sugar, red and processed meat, and sweets, cakes, and snacks was 5–126% higher, whereas intake of fiber, fruit and berries, vegetables, and dairy products was 7–17% lower on unusual than on normal days ( P < 0.001). The same pattern was seen for normal/unusual days during the weekdays, weekends and over time. Finally, 99% of the breast cancer patients used the free text fields to report additional intake with a mean energy of 1.1 MJ/day. Conclusion For breast cancer patients during the 12-month post-surgery period, unusual days are important drivers of total intake, especially for alcohol. The free text fields in the pre-coded food diary contributed substantially to the total intake.

Functional profiling of a cancer patient's tumor cells holds potential to tailor personalized cancer treatment. Here, we report the utility of fresh uncultured tumor-derived EpCAM(+) epithelial cells (FUTCs) for ex vivo drug response interrogation. Analysis of murine Kras mutant FUTCs demonstrates pharmacological and adaptive signaling profiles comparable to subtype-matched cultured cells. By applying FUTC profiling on non-small cell lung cancer patient samples, we report robust drug-response data in 19 of 20 cases, with cells exhibiting targeted drug sensitivities corresponding to their oncogenic drivers. In one of these cases, an EGFR mutant lung adenocarcinoma patient refractory to osimertinib, FUTC profiling is used to guide compassionate treatment. FUTC profiling identifies selective sensitivity to disulfiram and the combination of carboplatin plus etoposide, and the patient receives substantial clinical benefit from treatment with these agents. We conclude that FUTC profiling provides a robust, rapid, and actionable assessment of personalized cancer treatment options.

24.02.2020: Originalartikkel - Kvinner med kosmetiske brystimplantater som deltok i Mammografiprogrammet hadde lavere risiko for å få påvist brystkreft, men sykdommen ble oppdaget i et senere utviklingsstadium hos dem med implantat enn dem uten.

Women with implants who participated in BreastScreen Norway had a lower risk of detection of breast cancer, but more advanced disease upon diagnosis than those without implants. This may be due to the difficulty caused by implants in performing and interpreting the mammograms. The women should be informed about this before undergoing augmentation mammoplasty.

AbstractThe time after a breast cancer diagnosis is a potential period for making positive dietary changes, but previous results are conflicting. The main aim of the present study was to study breast cancer patients’ dietary changes during the 12 months post-surgery and from 12 months pre-surgery to 12 months post-surgery with repeated administration of a 7-d pre-coded food diary and an FFQ, respectively. Women (n 506), mean age 55·3 years diagnosed with invasive breast cancer (stages I and II), were included. The dietary intake was quite stable over time, but the intake was lower for energy (0·3 and 0·4 MJ/d), alcohol (1·9 and 1·5 g/d) and vegetables (17 and 22 g/d) at 6 months than 3 weeks post-surgery (food diary) and at 12 months post-surgery than pre-surgery (FFQ), respectively. Furthermore, energy percentage (E%) from carbohydrates increased between 0·8 and 1·2 E% and E% from fat decreased between 0·6 and 0·8 E% over time, measured by both dietary assessment methods. We observed a higher intake of dairy products (11 g/d) at 6 months post-surgery (food diary), and a lower intake of dairy products (34 g/d) and red and processed meat (7·2 g/d) at 12 months post-surgery (FFQ). Moreover, 24 % of the patients claimed they made dietary changes, but mostly they did not change their diet differently compared with those patients who claimed no changes. In conclusion, breast cancer patients reported only minor dietary changes from 12 months pre-surgery and during the 12 months post-surgery.

Abstract Background: Adjuvant breast cancer treatment may cause metabolic perturbations, such as dyslipidaemia, potentially exacerbating risk of cardiometabolic disease as well as risk of breast cancer recurrence. Physical exercise may have beneficial metabolic effects, but it’s effect on serum lipoprotein- and metabolite profiles during adjuvant breast cancer treatment including chemotherapy is not yet well established. Methods: The women participating in this pilot study of Energy Balance and Breast Cancer Aspects (EBBA)-II, were aged 38-69 years and diagnosed with stage I-II breast cancer. 60 breast cancer patients were randomized after surgery to a control group (n = 29, usual care) or an intervention group (n = 31, intervention), stratified by menopausal status. The patients in the intervention group received a detailed exercise program and met for supervised training sessions in groups of 10-12 women for 60 minutes twice a week during a 12 month period, and were in addition asked to perform at least 60 minutes of exercise at home (a total of 180 minutes of exercise weekly). Fasting serum samples were collected pre-surgery and after six months, and analysed by nuclear magnetic resonance (NMR)-spectroscopy and mass spectrometry. 170 metabolites and 109 lipoprotein subclass variables were quantified and analysed using orthogonalized partial least squares discriminant analysis. Statistical significance was assessed by permutation testing. Single variables were tested with Mann Whitney U-tests or multiple linear regression (NCT02240836). Results: The breast cancer patients (n = 60) had at pre-surgery the following means: Age at diagnosis of 55.4 years (38-69 years), low density lipoprotein (LDL)-cholesterol 145.4 mg/dl (3.76 mmol/L), high density lipoprotein (HDL)-cholesterol 70.4 mg/dl (1.82 mmol/L), and triglycerides 101.9 mg/dl (1.15 mmol/L), and 58.3 % of the patients underwent chemotherapy (paclitaxel/docetaxel/5-FU/epirubicin/cyclophosphamide based adjuvant chemotherapy). Physical exercise ameliorated chemotherapy-induced increases in very low density lipoprotein (VLDL)- and intermediate density lipoprotein (IDL)-associated lipids, and reduced triglyceride enrichment in LDL and HDL compared with chemotherapy controls (p = 0.003). Physical exercise also significantly increased apoA1 (4.6 % increase vs 11.3 % decrease, q = 0.02) and apoA2 (5.2 % increase vs 13.0 % decrease, q = 0.01) compared with chemotherapy control patients. The NMR-measured lipid signal at 1.55-1.60 ppm increased after six months in chemotherapy recipients, but this was attenuated among chemotherapy recipients in the intervention group. No statistically significant effect of physical exercise on serum levels of small-molecular metabolites was detected. Conclusion: Our findings suggest that physical exercise may prevent atherogenic alterations in lipoprotein profile induced by chemotherapy. The results indicate increased HDL particle number- and function, as well as increased triglyceride clearance in the intervention group. Thus, atherogenic alterations in lipoprotein profile may play a role in evaluating breast cancer treatment, and could potentially be biomarkers of importance for breast cancer prognosis and co-morbidity. Citation Format: Torfinn Støve Madssen, Vidar Gordon Flote, Inger Thune, Gro Falkener Bertheussen, Anders Husøy, Steinar Lundgren, Hanne Frydenberg, Erik Wist, Ellen Schlichting, Jon Lømo, Anne McTiernan, Tone Frost Bathen, Guro Fanneløb Giskeødegård. Lipoprotein and metabolite responses to physical exercise during adjuvant breast cancer treatment [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-13-01.

Abstract Background: Breast cancer survival rates have improved, but cardiovascular disease is a competing cause of death among breast cancer survivors, and treatment-induced cardio-toxicity remains a major concern. The effect of aerobic exercise on cardiovascular function during adjuvant breast cancer treatment is not yet well established. Material & methods: The women participating in the Energy Balance and Breast Cancer Aspect (EBBA)-II trial are aged 18-75 years and diagnosed with stage I-II breast cancer. VO2max was assessed at three separate times, prior to surgery and at 6 and 12 months after, using a maximum exercise test on a treadmill (modified Balke protocol).The patients were randomized after surgery to a control group (n=188, usual care) or an intervention group (n=187) stratified by menopausal status. The 12 months exercise intervention program started 2-3 weeks after surgery and the patients received a detailed training program based on their own VO2max at baseline. They met for training sessions in groups of 10-12 women for 60 minutes twice a week during a 12 month period, and were in addition asked to perform at least 120 minutes of exercise at home (a total of 240 minutes of exercise weekly).Analyses were done on an intention-to-treat basis (NCT02240836). Preliminary results: Breast cancer patients (n=375) with a mean age at diagnosis of 55.2 years (27.0-75.0 years) had a mean body mass index (BMI) of 25.1kg/m2, a mean VO2max before surgery of 31.5 ml•min−1•kg−1, and 57 % of the patients underwent chemotherapy (paclitaxel, epirubicin/cyclophosphamide based adjuvant chemotherapy). Comparing the intervention group to the control group, the intervention group had a decrease in VO2max of 2.7% after 6 months, but they improved their VO2max by 2.3 % at 12 months compared to before surgery (p=0.001). Breast cancer patients in the control group had a 10 % reduction in VO2max 6 months after surgery (p<0.001), and a 3.8% decrease in VO2max was observed at 12 months compared to before surgery (p<0.001). Among patients in the control group who received chemotherapy, a decline in VO2max by 5.3 ml•min−1•kg−1 (16.2%) (p<0.001) at 6 months was observed. This reduction in VO2max at 6 months was most pronounced in patients who received paclitaxel alone, or paclitaxel in combination with epirubicin/cyclophosphamide (6.1 ml•min−1•kg−1, 18.7% decrease). In comparison, patients in the intervention group who received chemotherapy had a decline of 2.4 ml•min−1•kg−1 (7.6%) in VO2max at 6 and after 12 months VO2max was equal to before surgery. Differences in VO2max at 6 and after 12 month between groups were in favor of the intervention group (p<0.05). Conclusion: Our findings strongly support that tailored exercise training during adjuvant breast cancer treatment may counteract a decline in cardiovascular function, and in particular among those receiving chemotherapy. Our study supports incorporation of supervised clinical exercise programs into breast cancer treatment guidelines. Final results of the trial at SABCS 2018 (the trial closes October 15, 2018) total included N=539 (NCT02240836) Citation Format: Thune I, Husøy A, Frydenberg H, Flote VG, Fjeldheim F, Bertheussen GF, Lundgren S, Lømo J, Wist EA, McTiernan A, Schlichting E. Cardiovascular function and the effect of exercise training during adjuvant breast cancer treatment. Results from The EBBA-II trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS5-02.