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Background: Invasive lobular carcinoma (ILC) represents up to 15% of all breast carcinomas. The majority of ILC express the estrogen receptor (ER) and have no amplification/overexpression of the human epidermal growth factor receptor 2 (HER2). A high body mass index (BMI) has been associated with an increased risk of developing ILC in postmenopausal women, similar to what is seen for breast cancer of no special type (NST). It is however unknown if BMI impacts the clinicopathological features and the prognosis of ILC. Methods: We performed a multicentric retrospective study in 5 European centers of patients diagnosed between January 2000 and December 2020 with ER+/HER2- non-metastatic pure (i.e., not mixed) ILC. Patient and tumor characteristics and event-related data were collected. BMI was categorized into underweight (≤18.5kg/m2), lean (>18.5kg/m2 and < 25kg/m2), overweight (≥25kg/m2 and < 30kg/m2) and obese (≥30kg/m2). The association of BMI as either a continuous or a categorical variable with clinicopathological variables was assessed using linear regression or ordinal logistic regression, respectively. Median follow-up was calculated using the reverse Kaplan-Meier estimator. Survival analyses using univariable (stratified by center) and multivariable (adjusted for all included variables and stratified by center) Cox regression were performed to evaluate the association of BMI with disease free survival (DFS), distant recurrence free survival (DRFS) and overall survival (OS). DFS and DRFS were analyzed in the presence of death without event as the competing risk. Results: The data of 2476 patients were collected and BMI was available for 2346 patients. In total, 1299 (55%) patients were lean, 638 (27%) overweight and 339 (14%) obese. Underweight patients only represented 3% of all patients and were thus excluded from further analyses. A higher age at diagnosis, higher grade, larger tumor size, nodal involvement and multifocality were significantly associated with higher BMI (Table 1). The median follow-up was 8,5 years (interquartile range 59.24 – 142.13 months). In univariable analysis, higher BMI was associated with worse survival outcomes (Table 2). However, this association was not seen in multivariable analysis while grade, tumor size and nodal involvement were still prognostic for all endpoints. Similar results were seen with BMI as a continuous variable. Conclusion: Larger tumors and nodal involvement were more likely to be found in patients with ER+/HER2- ILC with higher BMI which might be explained by a delayed diagnosis in these patients. Higher grade also seemed to be associated with higher BMI. In multivariable analyses, BMI was not found to be an independent prognostic factor. Tumor grade, tumor size, and nodal status remained strongly prognostic for survival outcomes in multivariable survival analyses which is consistent with their known prognostic importance in luminal tumors. We hypothesize that the prognostic effect of BMI is mediated through these variables for patients with ER+/HER2- ILC. Table 1. Association of clinicopathological features of ER+/HER2- ILC with categorical BMI. Table 2. Association of categorical BMI and other clinicopathological features of ER+/HER2- ILC with survival. Citation Format: Karen Van Baelen, Ha-Linh Nguyen, François Richard, Anne-Sophie Hamy, Aullène Toussaint, Fabien Reyal, Anne Salomon, Luc Dirix, Peter Vermeulen, Hilde Wuyts, Maria Karsten, Adam D. Dordevic, Guilherme Nader Marta, Evandro de Azambuja, Christos Sotiriou, Denis Larsimont, Ottavia Amato, Marion Maetens, Maxim De Schepper, Tatjana Geukens, Sileny Han, Thaïs Baert, Kevin Punie, Hans Wildiers, Chantal Remmerie, Ann Smeets, Ines Nevelsteen, Giuseppe Floris, Elia Biganzoli, Patrick Neven, Christine Desmedt. Association of body mass index with clinicopathological features and survival in patients with primary ER+/HER2- invasive lobular breast cancer [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 P3-05-40.

As wider insights are gained on the molecular landscape of triple-negative breast cancer (TNBC), novel targeted therapeutic strategies might become an option in this setting as well. Activating mutations ofPIK3CArepresent the second most common alteration in TNBC after theTP53mutation, with a prevalence of ∼10%–15%. Considering the well-established predictive role ofPIK3CAmutations for response to agents targeting the PI3K/AKT/mTOR pathway, several clinical trials are currently evaluating these drugs in patients with advanced TNBC. However, much less is known regarding the actionability ofPIK3CAcopy-number gains, which represent a thoroughly common molecular alteration in TNBC, with a prevalence estimated at 6%–20%, and are listed as “likely gain-of-function” alterations in the OncoKB database. In the present paper, we describe two clinical cases in which patients harboringPIK3CA-amplified TNBC received a targeted treatment with the mTOR-inhibitor everolimus and the PI3K-inhibitor alpelisib, respectively, with evidence of disease response on 18F-FDG positron-emission tomography (PET) imaging. Hence, we discuss the evidence presently available regarding a possible predictive value ofPIK3CAamplification for response to targeted treatment strategies, suggesting that this molecular alteration might represent an intriguing biomarker in this sense. Considering that few of the currently active clinical trials assessing agents targeting the PI3K/AKT/mTOR pathway in TNBC select patients based on tumor molecular characterization, and none of these based onPIK3CAcopy-number status, we urge for the introduction ofPIK3CAamplification as a criterion for patient selection in future clinical trials in this setting.

The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted.Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/- Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias.In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade ≥3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05).We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/- Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure.

About a half of HER2-negative breast cancer (BC) show HER2-low expression that can be targeted by new antibody-drug conjugates. The main aim of this study is to describe the evolution of HER2 expression from primary BC to relapse by including HER2-low category in both primary and recurrent BC samples. Patients with matched primary and relapse BC samples were included. HER2 was evaluated according to ASCO/CAP recommendations in place at the time of diagnosis. A cutoff of10% cells staining for HER2-positivity was applied. HER2-negative cases were sub-classified as HER2-low (IHC = 1 + /2+ and ISH not amplified), or HER2-0 (IHC-0). 547 patients were included. The proportion of HER2-low cases was 34.2% on the primary tumor and 37.3% on the relapse samples. Among HER2-negative cases, HER2-low status was more frequent in HR-positive vs triple-negative tumors (47.3% vs 35.4% on primary tumor samples, 53.8% vs 36.2% on relapse samples). The overall rate of HER2 discordance was 38.0%, mostly represented by HER2-0 switching to HER2-low (15%) and HER2-low switching to HER2-0 (14%). Among patients with a primary HER2-negative tumor, the rate of HER2 discordance was higher in HR-positive/HER2-negative vs triple-negative cases (45.5% vs 36.7% p = 0.170). This difference was mostly driven by cases switching from HER2-0 to HER2-low. HER2-low expression is highly unstable during disease evolution. Relapse biopsy in case of a primary HER2-0 tumor may open new therapeutic opportunities in a relevant proportion of patients.

About a half of HER2-negative breast cancer (BC) show HER2-low expression that can be targeted by new antibody-drug conjugates. The main aim of this study is to describe the evolution of HER2 expression from primary BC to relapse by including HER2-low category in both primary and recurrent BC samples. Patients with matched primary and relapse BC samples were included. HER2 was evaluated according to ASCO/CAP recommendations in place at the time of diagnosis. A cutoff of >10% cells staining for HER2-positivity was applied. HER2-negative cases were sub-classified as HER2-low (IHC = 1 + /2+ and ISH not amplified), or HER2-0 (IHC-0). 547 patients were included. The proportion of HER2-low cases was 34.2% on the primary tumor and 37.3% on the relapse samples. Among HER2-negative cases, HER2-low status was more frequent in HR-positive vs triple-negative tumors (47.3% vs 35.4% on primary tumor samples, 53.8% vs 36.2% on relapse samples). The overall rate of HER2 discordance was 38.0%, mostly represented by HER2-0 switching to HER2-low (15%) and HER2-low switching to HER2-0 (14%). Among patients with a primary HER2-negative tumor, the rate of HER2 discordance was higher in HR-positive/HER2-negative vs triple-negative cases (45.5% vs 36.7% p = 0.170). This difference was mostly driven by cases switching from HER2-0 to HER2-low. HER2-low expression is highly unstable during disease evolution. Relapse biopsy in case of a primary HER2-0 tumor may open new therapeutic opportunities in a relevant proportion of patients.

The novel coronavirus disease 2019 has grown to be a global public health emergency. The rapid spread of the infection has raised many questions in the oncohematological scientific community regarding the appropriateness of high‐dose chemotherapy with autologous stem cell transplantation (ASCT). We here report two cases of patients who received ASCT at our Institute during the epidemic in Italy, affected with Hodgkin lymphoma and germ cell tumor, respectively. The two patients underwent a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) on hospital admittance and during the period of bone marrow aplasia. They were attended to exclusively by dedicated health care staff who followed specifically implemented protocols for bedside nursing and care. They completed the procedure without unexpected side effect. Our experience demonstrates how ASCT can be performed safely if procedures are reorganized ad hoc to reduce the risk of SARS‐CoV‐2 infection., The COVID‐19 pandemic has raised many questions in the oncohematological scientific community about risks associated with transplant procedures. This article reports two patient cases, focusing on the risks of performing high‐dose chemotherapy with autologous peripheral blood stem cell transplantation during the COVID‐19 pandemic weighed against the expected clinical benefit.

Rhabdomyolysis is a common cause of acute kidney injury (AKI) that is usually triggered by trauma. However, less common causes of rhabdomyolysis may precipitate AKI as well, possibly representing a diagnostic challenge even for the experienced nephrologist. Genetic defects of muscle metabolism represent one of these causes and can be overlooked in adults, since these diseases usually become apparent in childhood. We present here a case in which an adult patient with severe exertional rhabdomyolysis leading to AKI was finally diagnosed with a genetic defect of lipid metabolism. A 41-year-old patient was brought to our attention because of AKI and pigmenturia after strenuous physical effort. At admission, the patient was over-hydrated with a weight increase of 3 kg in few days. Laboratory examination showed creatinine of 8.7 mg/dl, along with increased myoglobin and CPK. Urinalysis was positive for haemoglobin and proteins, while urinary sediment analysis did not demonstrate any red blood cell but rather “muddy-brown” casts and tubular cells. Urine output was forced and the patient completely recovered renal function. Genetic analysis later demonstrated the presence of a common mutation of Carnitine Palmitoyl-Transferase II (CPTII). When facing rhabdomyolysis of obscure origin, nephrologists must keep in mind the possibility that even adult patients may have a genetic defect of energy metabolism. In these cases, patients usually experience rhabdomyolysis during exertion, fasting, or infection. CPTII deficiency often has a subtle presentation and might be unrecognized until AKI develops. Therefore, it is important to consider a genetic defect of muscle metabolism even in adult patients when a history of rhabdomyolysis of unclear origin is present.