Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.

BACKGROUND: Invasive lobular breast cancer (ILC) is the second most common type of breast cancer after invasive breast cancer of no special type (NST), representing up to 15% of all breast cancers. DESIGN: Latest data on ILC are presented, focusing on diagnosis, molecular make-up according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) guidelines, treatment in the early and metastatic setting and ILC-focused clinical trials. RESULTS: At the imaging level, magnetic resonance imaging-based and novel positron emission tomography/computed tomography-based techniques can overcome the limitations of currently used imaging techniques for diagnosing ILC. At the pathology level, E-cadherin immunohistochemistry could help improving inter-pathologist agreement. The majority of patients with ILC do not seem to benefit as much from (neo-)adjuvant chemotherapy as patients with NST, although chemotherapy might be required in a subset of high-risk patients. No differences in treatment efficacy are seen for anti-human epidermal growth factor receptor 2 (HER2) therapies in the adjuvant setting and cyclin-dependent kinases 4 and 6 inhibitors in the metastatic setting. The clinical utility of the commercially available prognostic gene expression-based tests is unclear for patients with ILC. Several ESCAT alterations differ in frequency between ILC and NST. Germline BRCA1 and PALB2 alterations are less frequent in patients with ILC, while germline CDH1 (gene coding for E-cadherin) alterations are more frequent in patients with ILC. Somatic HER2 mutations are more frequent in ILC, especially in metastases (15% ILC versus 5% NST). A high tumour mutational burden, relevant for immune checkpoint inhibition, is more frequent in ILC metastases (16%) than in NST metastases (5%). Tumours with somatic inactivating CDH1 mutations may be vulnerable for treatment with ROS1 inhibitors, a concept currently investigated in early and metastatic ILC. CONCLUSION: ILC is a unique malignancy based on its pathological and biological features leading to differences in diagnosis as well as in treatment response, resistance and targets as compared to NST.

Breast cancer subtype and survival by parity and time since last birth.

BACKGROUND: Pregnancy affects breast cancer risk but how it affects the subtype and prognosis remain controversial. We studied the effect of parity and time since last birth on breast cancer subtype and outcome. PATIENTS AND METHODS: We conducted a retrospective multivariate cohort study including all premenopausal women with early breast cancer aged ≤ 50 years (N = 1306) at diagnosis at the University Hospitals Leuven (Jan. 2000-Dec. 2009). Primary study endpoints were the breast cancer subtype, disease-free survival, and distant disease-free survival by parity and time since last birth. Statistical methods used were baseline-category logits models and Cox proportional hazard models. Multivariable models were used to correct for possible confounders. RESULTS: Breast cancer subtypes did not differ between nulliparous (N = 266) and parous women (N = 1040) but subtypes differed significantly in parous women by time since last birth (p < 0.001). Tumors within 5 years of last birth were proportionally more likely triple negative and HER-2 like, even when corrected for age at diagnosis. After a mean follow-up period of 10 years, parous women had a better disease-free survival compared to nulliparous women (HR 0.733; CI 0.560-0.961; p = 0.025, HR 0.738; CI 0.559-0.974; p = 0.032 before and after correction for known prognostic factors, respectively). In parous women, a longer time since last birth was correlated with a longer disease-free survival compared to patients with a recent pregnancy (HR 0.976; CI 0.957-0.996; p = 0.018). However, after correction, this association completely disappeared (HR 1.010; CI 0.982-1.040; p = 0.480). CONCLUSION: We observed a better disease-free survival for parous than nulliparous women. The influence of recent birth on disease-free survival is probably due to tumor and patient characteristics, as recent birth is associated with more aggressive subtypes.

Expression patterns of H3K27me3 for differentiation of breast fibroadenomas and phyllodes tumors.

Phyllodes tumors (PTs) are rare breast tumors showing overlapping features with fibroadenomas (FAs). Diagnosis on small biopsies is challenging. New diagnostic markers are needed. Here we evaluated immunohistochemical staining of histone 3 trimethyl-lysine-27 (H3K27me3) as a diagnostic and prognostic marker in a series of PTs. Surgically removed PTs at our institution (September 1990 and July 2022) and control FAs. Tissue micro-arrays (4 cores, 2 mm Ø) stained with H3K27me3, and scored with QuPath-derived H-score. Fisher exact test, Mann-Whitney U-test and chi-squared test used for group comparison. ROC analysis applied to define cutoffs. Cox proportional hazards models were used for assessing disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS) in PTs. We included 81 patients with PTs and 44 patients with FAs. QuPath-derived H-scores of stromal H3K27me3 were statically significantly lower in PTs than in FAs (p < 0.001). We identified exploratory cutoffs to discriminate FAs from benign and malignant PTs (AUC = 0.78 and 0.73, respectively). No associations between DFS, OS, or DSS and H3K27me3 expression were found. H3K27me3 expression differs between FAs and PTs, indicating potential as diagnostic marker, but it is not predictive for DFS, OS or DSS in PTs. Further validation is needed.

Features of durable response and treatment efficacy for capecitabine monotherapy in advanced breast cancer: real-world evidence from a large single-centre cohort.

PURPOSE: In metastatic breast cancer (MBC) population treated with capecitabine monotherapy, we investigated clinical-pathological features as possible biomarkers for the oncological outcome. METHODS: Retrospective study of consecutive MBC patients treated at University Hospitals Leuven starting capecitabine between 1999 and 2017. The primary endpoint was the durable response (DR), defined as non-progressive disease for > 52 weeks. Other main endpoints were objective response rate (ORR), time to progression (TTP) and overall survival (OS). RESULTS: We included 506 patients; mean age at primary breast cancer diagnosis was 51.2 years; 18.2% had de novo MBC; 98.8% were pre-treated with taxanes and/or anthracycline. DR was reached in 11.6%. Patients with DR, as compared to those without DR, were more likely oestrogen receptor (ER) positive (91.5% vs. 76.8%, p = 0.010) at first diagnosis, had a lower incidence of lymph node (LN) involvement (35.6% vs. 49.9%, p = 0.039) before starting capecitabine, were more likely to present with metastases limited to ≤ 2 involved sites (54.2% vs. 38.5%, p = 0.020) and time from metastasis to start of capecitabine was longer (mean 3.5 vs. 2.7 years, p = 0.020). ORR was 22%. Median TTP and OS were 28 and 58 weeks, respectively. In multivariate analysis (only performed for TTP), ER positivity (hazard ratio (HR) = 0.529, p < 0.0001), HER2 negativity (HR = 0.582, p = 0.024), absence of LN (HR = 0.751, p = 0.008) and liver involvement (HR = 0.746, p = 0.013), older age at capecitabine start (HR = 0.925, p < 0.0001) and younger age at diagnosis of MBC (HR = 0.935, p = 0.001) were significant features of longer TTP. CONCLUSION: Our data display relevant clinical-pathological features associated with DR and TTP in patients receiving capecitabine monotherapy for MBC.

Ischaemic colitis after endovascular repair of an infrarenal abdominal aortic aneurysm: a case report.

INTRODUCTION: Endovascular repair of abdominal aortic aneurysms (EVAR) has proven to be an attractive and successful alternative to traditional open surgery in properly selected patients. As in open surgery, ischaemic colitis remains a feared complication, but the incidence and causes are not properly documented. OBJECTIVE: To present a case of endovascular aneurysm repair complicated by postoperative unilateral graft limb occlusion and ischaemic colitis. CASE REPORT: A 76-year-old woman presented with diffuse abdominal pain in the presence of an infrarenal abdominal aorta aneurysm of 5.5 cm. Based on CT and calibrated angiography, the patient was selected for endovascular repair which was performed with an Excluder bifurcation graft (W. L. Gore & Associates Inc., Newark USA). The endograft was placed successfully, but completion angiography showed a kinking of the left graft limb at the level of the aortic bifurcation. The patient developed acute ischaemia of the left limb 3 days postoperatively. Treatment consisted of femorofemoral cross-over graft. One week postoperatively she developed diarrhoea. A sigmoidoscopy was performed, showing ischaemic colitis grade I. In spite of the initial good result of conservative therapy, she had to undergo a left hemicolectomy with manual colorectal anastomosis and protective ileostomy 25 days later. Despite this intervention, the patient developed multiple organ failure and died after 2 months. CONCLUSION: Postoperative ischaemic colitis has been described in extenso after open aneurysm repair. The incidence after endovascular repair is not well described. From 1998 to 2005, we performed 52 endovascular procedures with a bifurcation endoprosthesis in the treatment of an infrarenal abdominal aortic aneurysm. We report one patient out of this series, who developed an ischaemic colitis after the procedure. Possible causes include cholesterol embolization and peroperative exclusion of the inferior mesenteric artery of which the consequences might be aggravated in our patient by subsequent thrombosis of the left graft limb.

Surgical interventions during STI 571 treatment of metastatic GIST: experience in six patients.

Gastrointestinal stromal tumours (GIST), previously classified as smooth muscle tumours, are the most common mesenchymal tumours of the digestive tract. Since the discovery of KIT (CD 117) expression, these tumours can be diagnosed confidently by pathology. Until recently, surgery was the only treatment available because these tumours were not sensitive to chemotherapy nor radiation therapy. In the long run most of these tumours recurred in the abdominal cavity or in the liver. Recently a new drug STI 573 (Glivec) showed very promising results in metastatic disease with response rates of about 65%. In six patients treated at our center, surgery was indicated during STI therapy because of subobstruction, skin necrosis, abdominal distention, bleeding. Surgery proved to be safe and efficient, allowing continuation of STI therapy in much better circumstances.