Gallen Consensus Research Articles

Frequency of HER2-Low in breast cancer biopsies in Chile.

e13163 Background: In breast cancer (BC), human epidermal growth factor receptor 2 (HER2) is a prognostic and predictive biomarker. Traditionally, the use of HER2-targeted therapies is reserved for BC that overexpress HER2, defined as immunohistochemical (IHC) expression of 3+ or 2+ with amplification of the gene encoding HER2, detected by in situ hybridization (ISH). Recently, the term HER2-Low, defined as the IHC expression of 1+ or 2+ with negative ISH, has gained relevance as a new predictive biomarker for the use of trastuzumab-deruxtecan. The frequency of HER2-Low BC in the Chilean population is unknown. The objective of this study is to show the frequency of HER2-Low BC in a Chilean center. Methods: Descriptive cross-sectional analysis of clinical records and biopsies of localized or metastatic invasive breast carcinoma performed at Clínica Santa María between January 2020 and December 2023. The IHC expression of the estrogen receptor (ER), progesterone receptor (PR), Ki-67, HER2, histological grade (G) and HER2 in situ hybridization (ISH) when appropriate. The frequency and characteristics of HER2-Low cases are described and compared with the surrogate clinicopathological subtypes luminal A, luminal B (HER2-Positive and Negative), HER2-Positive and Triple Negative (TN), according to the St Gallen Consensus Conference 2013. Results: Between January 2020 and December 2023, a total of 339 biopsies with invasive BC were identified, from which 104 (36.0%) met the definition of HER2-Low. The frequency of luminal B and luminal A that met the definition of HER2-Low was 54 (51.9%) and 40 (38.5%), respectively. Of the 253 biopsies classified as luminal, 94 (37.2%) met the definition of HER2-Low, while of the 36 biopsies classified as TN, 10 (27.8%) did. Luminal B HER2-Negative and TN surrogate subtypes that met the definition of HER2-Low had a higher frequency of G3 than their non-HER2-Low counterpart. Conclusions: In the population analyzed, a considerable percentage of cases meet the definition of HER2-Low. This has relevant therapeutic implications. Distribution of biopsies that meet HER2-Low criteria according to surrogate clinicopathological subtype of breast cancer. [Table: see text]

Treatment of Early Breast Cancer: The 18th St.Gallen International Breast Cancer Consensus Conference against the Background of Current German Treatment Recommendations.

This year's 18th St.Gallen (SG) consensus conference on the treatment of early breast cancer (SGBCC: St.Gallen International Breast Cancer Conference) focused on practice-oriented questions. The individual situation and risk-benefit assessment were discussed in great detail. As in previous years, a German working group of leading breast cancer experts presented the results of the international SGBCC2023 against the background of German treatment recommendations - especially the updated treatment recommendations of the Arbeitsgemeinschaft Gynäkologische Onkologie e. V. (AGO) - for everyday clinical practice in Germany. The German treatment recommendations of AGO are based on the current evidence. The comparison with the clinical approach in Germany has proven useful, as the SGBCC panel consists of experts from different countries and disciplines. That is why country-specific characteristics can be incorporated into the SGBCC recommendations.

Subtypes of high-grade breast ductal carcinoma in situ (DCIS): incidence and potential clinical impact

ObjectiveThe purpose of this study was to investigate and classify the molecular subtypes of high-grade ductal carcinoma in situ (DCIS) and identify possible high-risk subtypes. The heterogenicity of DCIS with variable clinical and histopathological presentations has been recognized. Nevertheless, only histopathological grading and diameter are currently implemented in clinical decision-making following the diagnosis of DCIS. The molecular subtypes of DCIS and their IHC surrogate markers have not been defined in conventional treatment guidelines and recommendations. We applied the definitions of molecular subtypes according to the IHC surrogate markers defined for IBC and subclassified high-grade DCIS, accordingly.MethodsHistopathological specimens were collected, revised, and regraded from 494 patients diagnosed with DCIS between 1996 and 2018. Other in situ and papillary lesions observed in breast biopsies were excluded from this study. 357 high-grade DCIS cases were submitted to IHC analysis. The markers investigated were ER, PR, HER2, and Ki67.Results45 cases were classified as grade 1, 19 as grade 2, and 430 as grade 3. Sixty patients with high-grade DCIS had an additional invasive component in the surgical specimen. Thirty-three patients were diagnosed with recurrent DCIS or invasive cancer (minimum one year after their primary DCIS diagnosis). The proportions of luminal A and luminal B HER2-negative subtypes varied depending on whether 2011 or 2013 St. Gallen Consensus Conference guidelines were adopted. Luminal A was the most prevalent subtype, according to both classifications. The luminal B HER2-positive subtype was found in 22.1% of cases, HER2-enriched subtype in 21.8%, and TPN subtype in 5.6%. There were strong indications that HER2-enriched subtype was significantly more frequent among DCIS with invasive component (p = 0.0169).ConclusionsHigh-grade DCIS exhibits all the molecular subtypes previously identified in IBC, but with a somewhat different distribution in our cohort. HER2-enriched subtype is substantially related to the presence of an invasive component in DCIS; consequently, it is regarded as a high-risk entity.

Primary therapy of early breast cancer: Egyptian view of 2021 St. Gallen consensus

PurposeThe theme of the St. Gallen International Breast Cancer Conference 2021 held virtually for the first time, due to the COVID-19 pandemic, was on tailoring therapies for patients with early breast cancer. A monkey survey that included an Egyptian Panel voted on most of the questions of the original St. Gallen consensus, and some added new questions most relevant to oncology practice in the country, to be able to compare voting results that reflect differences in breast cancer management and decision making.MethodsThe panel included 74 Egyptian scientists from different oncology specialties. Management issues including controversial diagnostic and therapeutic interventions were prepared by a small committee and then projected using the online monkey survey website: https://www.surveymonkey.com. The survey included 130 questions. Results were then analyzed, tabulated, and compared to the voting results of the original St. Gallen consensus.Results and conclusionsVoting questions and resulting percentages of answers from the Egyptian panel were summarized. There was no consensus between the Egyptian and the original St. Gallen panels on 28/130 statements. They mostly included genetic and pathologic aspects, specifically the routine use of gene signature assays and a few queries involving surgical, radiotherapeutic, and systemic interventions. Probably, available resources and healthcare system differences in Egypt compared to European and the USA were the cause of these differences. This would also be applicable to other low- and low-middle-income healthcare scenarios present in many countries, especially with the present constraints of the COVID-19 pandemic.

Characteristics of HER2-negative breast cancers with FISH-equivocal status according to 2018 ASCO/CAP guideline

BackgroundAccording to 2018 ASCO/CAP guideline, HER2 FISH-equivocal breast cancers will be categorized as HER2 negative except those with IHC 3+. However, whether or not HER2 FISH-equivocal breast cancers was a heterogeneous group has not been well illustrated.Methods195 HER2 FISH-equivocal breast cancer samples were collected from 2014 to 2018. The molecular subtype was identified according to 2013 St Gallen consensus, and HER2 status was also re-determined following 2018 ASCO/CAP guideline. All samples were classified into 4 groups according to the average HER2 copy number (4.0–4.4, 4.5–4.9, 5.0–5.4, 5.5–5.9 signals/cell). The relationship between HER2 copy number and clinicopathological parameters was analyzed.Results183 (93.8%) of 195 FISH-equivocal cases were classified as luminal-like subtype, while the other 12 (6.2%) were undetermined. Following 2018 ASCO/CAP guideline, all FISH-equivocal cases were recategorized as HER2 negative. Therefore, 31(15.9%) cases were luminal A-like, 152 (77.9%) were luminal B-like (HER2 negative) and 12 (6.2%) were triple negative. The average HER2 copy number showed a positive correlation with chromosome 17 polysomy, but had no significant association with other clinicopathological parameters as well as prognosis. 17 (8.7%) patients were treated with trastuzumab, but showed no difference in prognosis with those who didn’t receive targeted therapy.ConclusionsIn this study, all HER2 FISH-equivocal breast cancers were recategorized as HER2 negative according to 2018 ASCO/CAP guideline. Most of these patients were luminal B-like (HER2 negative). The average HER2 copy number had no significant association with clinicopathological parameters, as well as prognosis.

Subtipos del carcinoma luminal de mama según el consenso de Saint Gallen en un grupo de pacientes venezolanas

ResumenIntroducción. El cáncer de mama es la neoplasia maligna más frecuente en las mujeres de todo el mundo. Los distintos subtipos intrínsecos tienen pronósticos diferentes y su prevalencia varía significativamente según los criterios establecidos en el Consenso de Saint Gallen.Objetivo. Clasificar los subtipos luminales del carcinoma de mama en una población de pacientes venezolanas según los consensos de Saint Gallen del 2009, 2011, 2013 y 2015. Materiales y métodos. Se hizo un estudio retrospectivo en 209 pacientes con carcinoma ductal infiltrante de mama, atendidas en el Instituto de Oncología "Dr. Miguel Pérez Carreño" de Valencia, Venezuela.Resultados. La distribución de los subtipos luminal A y B cambió después de reclasificar los casos según los consensos de 2011, 2013 y 2015; el subtipo luminal B fue el más común en la serie de estudio.Conclusiones. Mediante la clasificación basada en los últimos criterios de Saint Gallen, se determinó un número mayor de tumores luminales B, lo que ayudaría a seleccionar a aquellas pacientes que no requieran la quimioterapia adyuvante y a quienes puedan beneficiarse de la terapia hormonal adyuvante en la práctica clínica.

The additional value of ONEST (Observers Needed to Evaluate Subjective Tests) in assessing reproducibility of oestrogen receptor, progesterone receptor, and Ki67 classification in breast cancer

The reproducibility of assessing potential biomarkers is crucial for their implementation. ONEST (Observers Needed to Evaluate Subjective Tests) has been recently introduced as a new additive evaluation method for the assessment of reliability, by demonstrating how the number of observers impact on interobserver agreement. Oestrogen receptor (ER), progesterone receptor (PR), and Ki67 proliferation marker immunohistochemical stainings were assessed on 50 core needle biopsy and 50 excision samples from breast cancers by 9 pathologists according to daily practice. ER and PR statuses based on the percentages of stained nuclei were the most consistently assessed parameters (intraclass correlation coefficients, ICC 0.918–0.996), whereas Ki67 with 5 different theoretical or St Gallen Consensus Conference–proposed cut-off values demonstrated moderate to good reproducibility (ICC: 0.625–0.760). ONEST highlighted that consistent tests like ER and PR assessment needed only 2 or 3 observers for optimal evaluation of reproducibility, and the width between plots of the best and worst overall percent agreement values for 100 randomly selected permutations of observers was narrow. In contrast, with less consistently evaluated tests of Ki67 categorization, ONEST suggested at least 5 observers required for more trustful assessment of reliability, and the bandwidth of the best and worst plots was wider (up to 34% difference between two observers). ONEST has additional value to traditional calculations of the interobserver agreement by not only highlighting the number of observers needed to trustfully evaluate reproducibility but also by highlighting the rate of agreement with an increasing number of observers and disagreement between the better and worse ratings.

Treatment of Patients with Early Breast Cancer: Evidence, Controversies, Consensus: German Expert Opinions on the 17th International St.Gallen Consensus Conference.

This yearʼs 17th St. Gallen (SG) Consensus Conference on the Treatment of Patients with Early Breast Cancer (SG-BCC) with the title “Customizing local and systemic therapies for women with early breast cancer” focused on the challenge of targeting the treatment of early breast cancer more specifically to the individual disease situation of each patient. As in previous years, a German working group of leading breast cancer experts discussed the results of the international SG-BCC 2021 in the context of the German guideline. It is helpful to compare the SG recommendations with the recently updated treatment recommendations of the Breast Commission of the German Working Group on Gynaecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie e. V., AGO) and the S3 guideline because the SG-BCC panel comprised experts from different countries, which is why country-specific aspects can be incorporated into the SG recommendations. The German treatment recommendations of the AGO and the S3 guideline are based on current evidence. Nevertheless, any therapeutic decision must always undergo a risk-benefit analysis for the specific situation and to be discussed with the patient.

Cancer Progress and Priorities: Breast Cancer.

Breast cancer is the most commonly diagnosed invasive cancer among women both globally and within the United States and the number one cause of cancer-related deaths among women globally ([1, 2][1]). Less than 1% of diagnosed breast cancers occur in men ([2][2]) and, therefore, male breast cancer is

Correlation of Breast Cancer Subgroups and Axillary Metastases with 18F-FDG PET/CT and the Contribution of 18F-FDG PET/CT in the Management of the Axilla.

To investigate whether breast and axilla maximum standard uptake (SUVmax) values contribute to the treatment approach in breast cancer subgroups. A descriptive study. University of Health Sciences/Adana City Training and Research Hospital, Turkey, from April 2017 to September 2019. Ninety patients, operated for early breast cancer, were examined histopathologically and demographically. Those patients were divided into subgroups, according to the St. Gallen consensus. Breast and axillary SUVmax uptakes of these subgroups were determined using (Fluorine18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). These values were compared with postoperative pathology results Results: The triple negative group had the highest values and the Luminal B pos (+) group had the lowest values, when the mean values of breast and axilla SUVmax were compared. Axilla SUVmax value in those with metastatic lymph node was 1.939 times higher than those without it. The cut-off value of SUVmax value of the axillary lymph nodes was found to be 1.1 in distinguishing metastatic from non-metastatic. As the biological aggressiveness of tumor increased, SUVmax values increased in parallel. As a result, SUVmax values guided in determining the presence of axillary metastasis and treatment strategy. Key Words: Breast cancer, 18F-FDG PET/ CT, SUVmax values, Tumor subgroups, Axilla.

Breast Cancer Treatment in the Era of Precision Medicine

Breast cancer is the most common cancer in women in the Western world. Treatment decisions in the adjuvant and metastatic setting are based on three immunohistochemistry markers, namely estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Based on the St. Gallen consensus, four distinct subtypes are defined: luminal A, luminal B, HER2-enriched and basal-like subtype breast cancer. In the era of precision medicine, more accurate profiling of breast cancer is now possible. Highly specific methods, including, but not limited to, next-generation sequencing (NGS), proteomics, and immune profiling, help to identify the targets for the appropriate treatment. Several international consortia trials, e.g., AURORA from the International Breast Cancer Study Group (IBCSG), are on the way to standardize optimal molecular treatment for breast cancer patients. This review gives you a clinically oriented overview of treatments for all breast cancer subtypes and an insight into molecular techniques and profile-based decisions. It is an overview from clinicians for clinicians.

Multigene testing in breast cancer: What have we learned from the 21-gene recurrence score assay?

Most invasive breast cancers express hormone receptors (HR) and typically have a favorable prognosis following endocrine therapy. Patients at a higher risk of recurrence can be identified by multigene prognostic classifiers such as the 21-gene recurrence score (RS) assay, 70-gene prognostic signature, PAM-50, 12-gene molecular score, and others. The 21-gene RS assay (Oncotype Dx™, Genomic Health, Redwood City, CA) has level I clinical evidence and is the most widely used multigene assay in North America. The RS assay is based on reverse transcriptase polymerase chain reaction that can be performed on the RNA isolated from formalin-fixed paraffin-embedded tissue. It evaluates the expression of 16 cancer-related genes developed based on a multi-step approach. Due to its ability to assess recurrence risk and predict potential benefit from chemotherapy, the assay is recommended for patients with node-negative, HR-positive, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer by the American Society of Clinical Oncology, National Comprehensive Cancer Network clinical practice guidelines in oncology, European Society for Medical Oncology clinical practice guidelines, and St. Gallen consensus panel guidelines. The RS assay has also been incorporated in the prognostic stage groups in the 8th edition of the American Joint Commission of Cancer staging manual in order to provide essential genomic information for optimal treatment decisions. This review will focus on the utility of the RS assay in HR-positive and HER2-negative breast cancer patients, including risk of distant and locoregional recurrence in node-negative and node-positive tumors, association with radiotherapy, special subtypes of breast cancer, practical issues related to selecting tumors for testing, and overview of the recently published TailorX (Trial Assigning IndividuaLized Options for treatment [Rx]) results.

Do YOU know the Ki-67 index of your breast cancer patients? Knowledge of your institution’s Ki-67 index distribution and its robustness is essential for decision-making in early breast cancer

ObjectivesThe proliferative activity of the Ki-67 index is important in decision-making of adjuvant treatments in early breast cancer. Its reliability can be reduced by inter-observer variability. This analysis’ objective is to evaluate the robustness of Ki-67 values within one center over 5 years and to compare its distribution with a published dataset. Materials and methodsKi-67 indices of early breast cancers treated at St. Gallen Breast Center were collected (2010–2014; 1154 patients). Distribution of Ki-67 values was analyzed for each year, along with histologic subtype and grading. Tumors were classified into intrinsic subtypes using two definitions: 2013 St. Gallen Consensus and the refined definition by Maisonneuve (“Milano Group”). Our institution’s Ki-67 cut-off value was adjusted to obtain the same distribution of luminal subtypes as published data of the Milano Group. ResultsKi-67 index frequency distributions were comparable between years (mean 26–30%, median 22–26%). Shape and position of the distribution curves were nearly identical. Ki-67 values correlated with tumor grade (median Ki-67: G1: 12.0%, G2: 21%, G3: 38%). Standard deviation of Ki-67 increased with higher grading (G1: 6.9; G2: 9.2; G3: 18.2; p < 0.001). According to the 2013 definition (and refined definition respectively), there were 35% (41%) luminal A-like and 65% (59%) luminal B-like tumors. To obtain the same distribution as the Milano group, Ki-67 cut-off needed to be elevated to 22%. ConclusionsKi-67 index assessment was comparable over many years. Knowledge of one’s institution’s Ki-67 value distribution is essential for clinical decision-making of adjuvant therapies in early breast cancer.

Abstract P6-11-03: Characteristics and survival outcomes of HIV-positive breast cancer patients: A systematic review and meta-analysis

Abstract Background: The number of people living with HIV is increasing worldwide thanks to the use of effective antiretroviral therapy. As these individuals get older, their risk of being diagnosed with cancer increases, including non-AIDS defining cancers such as breast cancer (BC). Most reports reveal that HIV+ patients (pts) with BC tend to be younger than HIV-uninfected (HIV-) pts. However, epidemiological data is yet conflicting regarding tumor stage at diagnosis, distribution of BC subtypes and overall survival (OS) of HIV+ pts as compared to HIV- pts. This meta-analysis aims to assess differences of baseline clinicopathological characteristics and OS of HIV+ vs HIV- BC pts. Methods: We performed a systematic review using MEDLINE, Scielo, and conference abstracts up to June 10, 2019, with no language restrictions. Cohort studies and consecutive series comparing baseline characteristics (age, stage at diagnosis or BC subtypes) and/or OS of HIV+ vs HIV- BC pts were included. BC subtypes were defined according to 2 classifications: 1) “classic” immunohistochemical (IHC) subtypes (ER+/HER2-; HER2+; triple-negative BC); 2) surrogate intrinsic subtypes as per the St. Gallen Consensus (luminal A-like, luminal B-like, HER2-enriched and basal-like). Summary risk estimates (pooled mean ratios [pMR] and odds ratios [pOR]) and 95% confidence intervals (CI) were calculated using random effects models. OS data were pooled as hazard ratios (HR) and 95% CI and modeled using a random effects model. The main endpoints were age (as a continuous variable), stage at diagnosis (early [0-II] vs late [III-IV]), distribution of BC subtypes and OS (using both adjusted and unadjusted HR). Subgroup analysis of each endpoint was performed according to region of the world. Results: A total of 16 studies (4 from North America and 12 from Sub-Saharan Africa [SSA]) published from 2005-2019 were included in this meta-analysis (with 1,764 HIV+ and 1,330,122 HIV- pts). HIV+ pts were younger than HIV- pts (pooled mean age of 41.1 vs 50.5 years, respectively; pMR 0.82, 95% CI 0.76-0.90, p &amp;lt; 0.001) and had a 45% increased risk of presenting with late stage disease (pOR 1.45, 95% CI 1.25-1.68, p &amp;lt; 0.001). There were no differences regarding distribution of BC subtypes, both by the “classic” IHC or by the St. Gallen classification. Overall, HIV+ pts had a 91% increased risk of dying as compared to HIV- pts (adjusted HR for OS: 1.91, 95% CI 1.06-3.45, p = 0.031 and unadjusted HR for OS: HR 1.47, 95% CI 1.10-1.95, p = 0.008). Subgroup analysis of OS according to region of the world showed that, in North America, HIV+ pts had a significantly increased risk of dying as compared to HIV- pts (adjusted HR 2.96, 95% CI 1.06-8.25, p = 0.038). In SSA, the increased mortality risk among HIV+ pts was also significant (adjusted HR 1.59, 95% CI 1.26-2.00, p &amp;lt; 0.001). Sensitivity analysis showed similar findings. Conclusion: This meta-analysis provides for the first time a comprehensive comparison of baseline characteristics and survival outcomes between HIV+ vs HIV- BC pts. Our results consistently demonstrate that HIV+ pts are diagnosed with BC at a younger age and at a more advanced stage. Additionally, even after adjusting for known prognostic factors, HIV+ pts have a worse OS as compared to HIV- pts, not only in developing countries (SSA) but also and particularly in developed countries (North America). There were no apparent differences in terms of distribution of BC subtypes. These results should raise the awareness of clinicians and policy makers regarding the detection and survival gap among HIV+ BC pts. This underserved population should be the focus of more research efforts, in order to better understand the reasons behind these disparities, which can be related to the HIV infection itself, to a more aggressive BC biology, and/or to a lower access to timely diagnosis and effective treatment. Citation Format: Mariana Brandão, Marco Bruzzone, Maria Alice Franzoi, Claudia De Angelis, Daniel Eiger, Rafael Caparica, Martine Piccart-Gebhart, Laurence Buisseret, Marcello Ceppi, Evandro de Azambuja, Matteo Lambertini. Characteristics and survival outcomes of HIV-positive breast cancer patients: A systematic review and meta-analysis [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 P6-11-03.

Abstract P3-08-02: The impact of breast cancer treatment concordance on survival in relation to comorbidity burden

Abstract Background: Patients with breast cancer (BC) and concomitant comorbidity have poorer disease prognosis, which may be related to a reduction in the receipt of curative cancer treatment. This study sought to determine the survival impact of BC treatment concordance in relation to comorbidity burden. Methods: Incident cases of unilateral stage I-III BC diagnosed between 2000 and 2015 were identified from a prospectively collected New Zealand BC register. Comorbidity severity was measured by C3 index score; derived via linkage with national hospitalization data. Treatment concordance (for breast and axillary surgery, adjuvant radiotherapy, adjuvant chemotherapy and endocrine therapy) was assigned in relation to minimum treatment indications as per national tumor standards and St Gallen Consensus Statements from relevant years. Multiple imputation of missing data was performed. Propensity scores for the conditional probability of receiving each treatment modality were modelled and used to create inverse probability of treatment- (IPTW) and standardized mortality ratio-weighted (SMRW) samples which were balanced with respect to baseline confounding variables between treated and untreated groups. For each treatment modality, weighted Cox proportional hazards (for all-cause mortality) and competing risks regression models (for BC-specific mortality) were produced, giving hazard ratio's (HR's) and sub-distribution hazard ratio's (SHR's) respectively as estimates of the average treatment effect (ATE) in IPTW samples and the average treatment effect on the treated in SMRW samples. Treatment effect heterogeneity by comorbidity severity was evaluated through the use of interaction tests and confirmatory subgroup analysis. Results: A total of 12,834 patients were included, with 21.5% possessing one or more pre-existing comorbidities. Patients with comorbidity were less likely to receive all four modalities of breast cancer treatment. Comorbidity burden was associated with poorer age and stage-adjusted survival, with greater impact on all-cause than BC-specific mortality. Overall, and for patients without comorbidity, those who received guideline-concordant treatments experienced significant reductions in all-cause and BC mortality risk (Tables 1 and 2; ATE’s from IPTW samples shown only). Heterogeneity in ATE’s by comorbidity severity was noted for surgery (BC mortality, p=.03) and endocrine therapy (all-cause mortality, p=.003), with lesser benefit at higher levels of comorbidity. Amongst patients with the greatest comorbidity severity (C3 score &amp;gt;2.00), surgery to the breast and axilla reduced the risk of all-cause but not BC mortality, with no mortality benefits obtained from the addition of adjuvant therapies. Conclusions: Patients with BC and concurrent comorbidity do not obtain the same survival benefits from guideline-concordant treatment as their non-comorbid counterparts. The inferior survival of such patients is therefore likely to be mediated through mechanisms other than reduced receipt of curative treatment. IPTW Cox regression: all-cause mortality for treatment concordance by comorbidity burdenBreast &amp; axillary surgeryAdjuvant radiotherapyAdjuvant chemotherapyEndocrine therapyC3 index categoryHR (95% CI)HR (95% CI)HR (95% CI)HR (95% CI)Overall0.52 (0.43-0.63)0.58 (0.48-0.69)0.77 (0.62-0.95)0.68 (0.59-0.79)00.50 (0.39-0.64)0.56 (0.45-0.69)0.74 (0.58-0.94)0.59 (0.49-0.71)1 (0.1-2.00)0.45 (0.31-0.65)0.61 (0.39-0.98)0.91 (0.56-1.47)0.84 (0.59-1.20)2 (&amp;gt;2.00)0.55 (0.41-0.74)0.69 (0.46-1.01)1.00 (0.52-1.89)0.97 (0.74-1.26) IPTW competing risks regression: BC mortality for treatment concordance by comorbidity burdenBreast &amp; axillary surgeryAdjuvant radiotherapyAdjuvant chemotherapyEndocrine therapyC3 index categorySHR (95% CI)SHR (95% CI)SHR (95% CI)SHR (95% CI)Overall0.43 (0.34-0.56)0.58 (0.46-0.73)0.83 (0.65-1.07)0.57 (0.47-0.72)00.40 (0.29-0.54)0.56 (0.43-0.73)0.78 (0.59-1.03)0.70 (0.44-0.73)1 (0.1-2.00)0.38 (0.21-0.69)0.62 (0.33-1.15)1.22 (0.70-2.13)0.47 (0.28-0.78)2 (&amp;gt;2.00)0.87 (0.47-1.58)0.77 (0.43-1.36)0.97 (0.42-2.23)1.21 (0.66-2.19) Citation Format: Melissa J Edwards, Ross A Lawrenson, Ian D Campbell. The impact of breast cancer treatment concordance on survival in relation to comorbidity burden [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 P3-08-02.

Abstract P1-18-10: Preoperative treatment of HER2-positive breast cancer in South Sweden. A retrospective, comprehensive survey of neo-adjuvant treated HER2-positve breast cancer in the SCAN-B project 2010-2017

Abstract Introduction: Over the last few years, neoadjuvant therapy has become a standard of care in HER2-positive early breast cancer. This standard has recently been confirmed by the St. Gallen Consensus for stage II and III HER2-positive disease. In neoadjuvant treatment adding anti HER2 treatment almost doubled the pathological complete response (pCR) rate. Later studies have shown a better outcome for patients achieving a pCR compared with those with a non-pCR. The aim of this study is to present a comprehensive description of preoperative treatment in HER2-positive, according to ASCO and Swedish guidelines, breast cancer with detail treatment routines, choice of drugs and regimens as well as adherence to national guidelines and treatment changes over time. Material: During the period October 2010 to December 2017 6572 patients with early breast cancer were diagnosed in the Skåne region of South Sweden and included in the SCAN-B project (Sweden Cancerome Analysis Network - Breast project, ClinicalTrials.gov identifier NCT02306096). The SCAN-B project is a population based study that during the period included 76.7% of all primary breast cancer patients in the catchment area. The majority of all tumors have been analyzed by NGS-based RNA sequencing, RNAseq. Results: Of the 6572 patients 672 (10.2%) were HER2 positive and of these 101 (15%) were treated in a neoadjuvant setting with chemotherapy and HER2 directed antibodies. The proportion of HER2-positive patients receiving neoadjuvant treatment with trastuzumab increased from 9% in 2010 to 29% in 2017. Patient age was 27 to 89 years, median age 54 years. Pertuzumab was introduced in 2016 and in 2017 85% of patients received the combination of trastuzumab and pertuzumab. At diagnosis tumor stage T1, T2, T3 and T4d was 19%, 60%, 14% and 5% respectively and 50% were node negative at sentinel node biopsy pre treatment. Of tumors 52% were estrogen receptor positive (ie &amp;gt;10% stained nuclei). During the neoadjuvant treatment period 31 patients were hospitalized at median 2 times for toxicity and a total of medium 4.7 days. At surgery 62% had a mastectomy and 38% breast conserving surgery. Follow up time is median 3.9 years and overall survival 94%. Conclusions: This retrospective analysis of neoadjuvant treated HER2-positive breast cancer patients shows a gradual increase of neoadjuvant treatment and a very fast implementation of pertuzumab when it became available in Sweden. Overall survival is high but the follow up time is short and the material to small to analyze subgroups. Data on tumor RNAseq will be presented. Citation Format: Martin Malmberg, Christer Larsson, Johan Vallon-Christersson, Anna Ehinger, Cecilia Hegardt, Fredrika Killander, Lisa Ryden, Lao H. Saal, Niklas Loman, Åke Borg. Preoperative treatment of HER2-positive breast cancer in South Sweden. A retrospective, comprehensive survey of neo-adjuvant treated HER2-positve breast cancer in the SCAN-B project 2010-2017 [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 P1-18-10.

Clinical and laboratory criteria used for patient selection for adjuvant chemotherapy in post-operative breast cancer

Introduction: Breast cancer remains the second most common type of cancer in the world and the first among women, with breast cancer incidence rates doubling in the last thirty years. In 2013, the St Gallen Consensus recommended the use of a study of the multigene profile and phenotyping to indicate adjuvance by use of the MammaPrint and Oncotype4 applications; however, as they are not available in the Unified Health System (Sistema Único de Saúde–SUS), clinical predictive criteria and laboratory tests are used for indication of adjuvant therapy. Objective: Evaluation of clinical and laboratory criteria in the selection of patients with breast cancer after surgery for adjuvant chemotherapy and quantification of the factors used in the selected patients and their results. Method: This is a retrospective, cross-sectional observational study with patients over 18 years of age, without gender and race restriction, diagnosed with breast cancer at a public hospital in São Paulo, from 09/10/18 to 10/12/18, who underwent surgical treatment and discussed adjuvant therapy. Patients with metastatic neoplasia and/or undergoing neoadjuvant treatment were excluded. Data collected were: TNM staging, histological type and hormone receptors, age and comorbidities in all medical records collected. Results: 1,390 consultations were carried out, with 42 patients selected, according to the study criteria. Since 40% of the patients were outside the recommended range for breast cancer screening, regarding TNM, late diagnoses were evidenced, with 69% presenting ≥T2 and 36% with lymph node involvement. Of the 42 patients, 98% received adjuvant therapy. Conclusion: It was evidenced by Paik et al., that 92.1% of the 668 patients enrolled in the NSABP B-14 study were considered of intermediate or high risk according to the NCCN and St. Gallen criteria, and by Oncotype DX, 50.6% of the patients were classified as at low risk of recurrence. However, as these are not available in SUS, the present study shows the need to use clinical and laboratory factors to indicate adjuvant therapy, and with these, of the 42 patients, 98% had indication, showing that they are not such effective means in the use of genetic tests, and patients treated by SUS initiate their treatments late, which impacts disease-free survival, since less than 10% of patients received care with early stage neoplasia.

Aldehyde dehydrogenase-1 positivity is associated with ER negativity in patients with invasive ductal carcinoma of the breast.

Cancer stem cells (CSCs) are self-renewable and can be differentiated into different cell types. They play an important role in oncogenic signaling pathways, tumor cell heterogeneity, metastasis, and therapeutic resistance. Aldehyde dehydrogenase 1 (ALDH1) was identified as a specific marker for breast CSCs. The study included a total of 105 patients with a diagnosis of invasive ductal carcinoma (IDC) who underwent mastectomy and with sufficient pathology material for histopathological examination. Patient demographics, tumor location, tumor diameter, the presence of lymphovascular and perineural invasion and lymph node metastasis, surgical margin status, and immunohistochemistry (IHC) staining results were obtained from patients' records. The tumors were classified into IHC-based molecular subtypes according to the St. Gallen Consensus Conference in 2013. A four-tiered scoring system was used based on ALDH1 staining percentage in tumor cells. The tumor was determined as positive if the score was 2 or higher. Clinical, histopathological findings, and ALDH1 staining results were correlated. Twenty-five cases (23.8%) were ALDH1 positive. The ALDH1 positive group compared to the negative group was found to be associated with ER negativity (p = 0.044), but there was no correlation with other clinical and histopathological findings. ALDH1-positive IDCs may be less sensitive to hormonal therapy and associated with aggressive behavior.

Systemic treatment of patients with early breast cancer: recent updates and state of the art

This review is focused on trials generating results that potentially impacted clinical practice since the 2017 St. Gallen Consensus; the most impactful trial was KATHERINE, which revealed a 11.3% absolute iDFS improvement with T-DM1 (compared to trastuzumab) in HER2-positive breast cancer patients who presented invasive residual disease following neoadjuvant treatment. These results, if reinforced by a subsequent overall survival benefit, will consolidate neoadjuvant treatment as the standard-of-care for most HER2-positive breast cancer patients. The addition of pertuzumab to adjuvant trastuzumab (APHINITY) or extending anti-HER2 therapy with 1 year of neratinib (ExteNET) also improved outcomes, but in a more modest way. In triple-negative early breast cancer patients presenting invasive residual disease after neoadjuvant chemotherapy, the CREATE-X trial demonstrated the benefit of post-neoadjuvant capecitabine. In patients with luminal tumours, updated results of the SOFT/TEXT trials confirmed the benefit of aromatase inhibitors plus ovarian suppression in high-risk premenopausal patients, and the 12-year results of the BIG1–98 trial demonstrated a sustained trend in favour of letrozole compared to tamoxifen in the adjuvant treatment of postmenopausal patients. The TAILOR-X study showed that, overall, patients with an intermediate recurrence risk score (11–25) in the OncotypeDX 21-gene assay did not benefit from adjuvant chemotherapy. A meta-analysis performed by the EBCTCG demonstrated that extended adjuvant aromatase inhibitors modestly reduced breast cancer recurrence risks, with a more pronounced benefit in patients previously treated with tamoxifen. Finally, an EBCTCG meta-analysis including patients with all breast cancer subtypes showed that dose-dense chemotherapy improved survival when compared to conventionally-timed chemotherapy.

Emerging strategies in neoadjuvant treatment of patients with HER2-positive early breast cancer

The St. Gallen Consensus 2017 recommended neoadjuvant therapy as a standard of care in stage II-III HER2-positive (HER2+) early breast cancer (EBC). Today, the neoadjuvant approach has become even more clinically relevant, as pathological complete response (pCR) status can not only be used to predict patient outcome, but also to escalate anti-HER2 therapy after surgery, based on the recently published results from the KATHARINE trial. Based on the NEOSPHERE results, dual antibody blockade together with chemotherapy has become the neoadjuvant standard. The chemotherapy backbone consists either of an anthracycline-taxane sequence or of an anthracycline-free regimen such as docetaxel and carboplatin. Adjuvant anti-HER2 therapy is then chosen based on initial tumor burden and pCR status. A multidisciplinary approach right from the beginning guarantees optimal treatment results for patients with HER2+ EBC.Emerging strategies will include early response markers (e.g. biomarkers, molecular imaging) as well as novel targeted agents (e.g. immunotherapy) in order to individualize systemic therapy in HER2-positive EBC. Neoadjuvant and adjuvant therapy thus represent components of an integrated, continuous strategy in HER2+ EBC allowing therapy adaptation according to individual tumor response. Refining the treatment algorithm with further de-escalation and escalation approaches will hopefully lead to better chances for cure as well as reduced short- and long-term toxicities in HER2-positive early breast cancer.