Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer.

Importance: The association of tumor-infiltrating lymphocyte (TIL) abundance in breast cancer tissue with cancer recurrence and death in patients with early-stage triple-negative breast cancer (TNBC) who are not treated with adjuvant or neoadjuvant chemotherapy is unclear.

Objective: To study the association of TIL abundance in breast cancer tissue with survival among patients with early-stage TNBC who were treated with locoregional therapy but no chemotherapy.

Design, Setting, And Participants: Retrospective pooled analysis of individual patient-level data from 13 participating centers in North America (Rochester, Minnesota; Vancouver, British Columbia, Canada), Europe (Paris, Lyon, and Villejuif, France; Amsterdam and Rotterdam, the Netherlands; Milan, Padova, and Genova, Italy; Gothenburg, Sweden), and Asia (Tokyo, Japan; Seoul, Korea), including 1966 participants diagnosed with TNBC between 1979 and 2017 (with follow-up until September 27, 2021) who received treatment with surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy.

Ki67 assessment protocol as an integral biomarker for avoiding radiotherapy in the LUMINA breast cancer trial.

Aims: The LUMINA trial demonstrated a very low local recurrence rate in women ≥55 years with low-risk luminal A breast cancer (defined as grade I-II, T1N0, hormone receptor positive, HER2 negative and Ki67 index ≤13.25%) treated with breast-conserving surgery and endocrine therapy (but no other systemic therapy), supporting the safe omission of radiation in these women. Here we describe the protocol for Ki67 assessment, the companion diagnostic used to guide omission of adjuvant radiotherapy.

Recent Advances in Optimizing Radiation Therapy Decisions in Early Invasive Breast Cancer.

Adjuvant whole breast irradiation after breast-conserving surgery is a well-established treatment standard for early invasive breast cancer. Screening, early diagnosis, refinement in surgical techniques, the knowledge of new and specific molecular prognostic factors, and now the standard use of more effective neo/adjuvant systemic therapies have proven instrumental in reducing the rates of locoregional relapses. This underscores the need for reliably identifying women with such low-risk disease burdens in whom elimination of radiation from the treatment plan would not compromise oncological safety.

Heterogeneity of triple negative breast cancer: Current advances in subtyping and treatment implications.

As the field of translational 'omics has progressed, refined classifiers at both genomic and proteomic levels have emerged to decipher the heterogeneity of breast cancer in a clinically-applicable way. The integration of 'omics knowledge at the DNA, RNA and protein levels is further expanding biologic understanding of breast cancer and opportunities for customized treatment, a particularly pressing need in clinically triple negative tumors. For this group of aggressive breast cancers, work from multiple groups has now validated at least four major biologically and clinically distinct omics-based subtypes.

Neither Tumor-Infiltrating Lymphocytes nor Cytotoxic T Cells Predict Enhanced Benefit from Chemotherapy in the DBCG77B Phase III Clinical Trial.

Recent studies have shown that immune infiltrates in the tumor microenvironment play a role in response to therapy, with some suggesting that patients with immunogenic tumors may receive increased benefit from chemotherapies. We evaluated this hypothesis in early breast cancer by testing the interaction between immune biomarkers and chemotherapy using materials from DBCG77B, a phase III clinical trial where high-risk premenopausal women were randomized to receive chemotherapy or no chemotherapy. Tissue microarrays were evaluated for tumor-infiltrating lymphocytes (TILs) assessed morphologically on hematoxylin and eosin-stained slides, and by immunohistochemistry for CD8, FOXP3, LAG-3, PD-1 and PD-L1.

Prognostic Significance of CSF-1R Expression in Early Invasive Breast Cancer.

Colony-stimulating factor-1 receptor (CSF-1R) signaling promotes an immune suppressive microenvironment enriched in M2 macrophages. Given that CSF-1R inhibitors are under investigation in clinical trials, including in breast cancer, CSF-1R expression and association with immune biomarkers could identify patients who derive greater benefit from combination with immunotherapies. TIMER2.

Proteomics-derived basal biomarker DNA-PKcs is associated with intrinsic subtype and long-term clinical outcomes in breast cancer.

Precise biomarkers are needed to guide better diagnostics and therapeutics for basal-like breast cancer, for which DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has been recently reported by the Clinical Proteomic Tumor Analysis Consortium as the most specific biomarker. We evaluated DNA-PKcs expression in clinically-annotated breast cancer tissue microarrays and correlated results with immune biomarkers (training set: n = 300; validation set: n = 2401). Following a pre-specified study design per REMARK criteria, we found that high expression of DNA-PKcs was significantly associated with stromal and CD8 + tumor infiltrating lymphocytes.

The immune microenvironment and relation to outcome in patients with advanced breast cancer treated with docetaxel with or without gemcitabine.

Preclinical studies suggest that some effects of conventional chemotherapy, and in particular, gemcitabine, are mediated through enhanced antitumor immune responses. The objective of this study was to use material from a randomized clinical trial to evaluate whether patients with preexisting immune infiltrates responded better to treatment with gemcitabine + docetaxel (GD) compared to docetaxel alone. Formalin fixed, paraffin-embedded breast cancer tissues from SBG0102 phase 3 trial patients randomly assigned to treatment with GD or docetaxel were used.

Granulocyte Colony Stimulating Factor Expression in Breast Cancer and Its Association with Carbonic Anhydrase IX and Immune Checkpoints.

Purpose: Granulocyte colony-stimulating factor (G-CSF) and hypoxia modulate the tumour immune microenvironment. In model systems, hypoxia-induced carbonic anhydrase IX (CAIX) has been associated with G-CSF and immune responses, including M2 polarization of macrophages. We investigated whether these associations exist in human breast cancer specimens, their relation to breast cancer subtypes, and clinical outcome.

Lack of Androgen Receptor Expression Selects for Basal-Like Phenotype and Is a Predictor of Poor Clinical Outcome in Non-Metastatic Triple Negative Breast Cancer.

Androgen receptor (AR) has emerged as a significant favorable prognostic indicator in estrogen receptor expressing (ER) breast cancer (BCa); however, its clinical and biological relevance in triple negative breast cancer (TNBC) and association with cancer stem cell (CSC) markers remain ambiguous. We examined the immunohistochemical expression of AR in a cohort of stage I-III TNBC cases ( = 197) with a long-term clinical follow-up data (mean follow-up = 53.6 months).

Expression of Androgen Receptor and Cancer Stem Cell Markers (CD44/CD24 and ALDH1): Prognostic Implications in Invasive Breast Cancer.

Background: Androgen receptor (AR) has emerged as a significant prognostic marker in early breast cancer (BCa). Association of AR with cancer stem cell (CSC) markers in BCa is unknown. Aim of the present study was to evaluate the immunohistochemical expression of AR, CD44, CD24 and ALDH1 in a cohort of Pakistani patients diagnosed with invasive BCa and to correlate the expression with 5- year disease free survival.

Antibacterial screening of traditional herbal plants and standard antibiotics against some human bacterial pathogens.

Chloroformic and isoamyl alcohol extracts of Cinnnamomum zylanicum, Cuminum cyminum, Curcuma long Linn, Trachyspermum ammi and selected standard antibiotics were investigated for their in vitro antibacterial activity against six human bacterial pathogens. The antibacterial activity was evaluated and based on the zone of inhibition using agar disc diffusion method. The tested bacterial strains were Streptococcus pyogenes, Staphylococcus epidermidis, Klebsiella pneumonia, Staphylococcus aurues, Serratia marcesnces, and Pseudomonas aeruginosa.

Lower incidence but more aggressive behavior of right sided breast cancer in Pakistani women: does right deserve more respect?

Background: The aim of this epidemiological study was to establish the laterality of breast cancer (BC) and its association with size, receptor status of the primary tumor and bone metastasis (BM) in a local population.

Materials And Methods: This retrospective study included cases of BC from Jan-2009 to Dec-2011 who were referred for metastatic work up or follow up survey with Technetium-99m MDP bone scan (BS) to the Nuclear Medicine Department of Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN). A total of 384 patients out of 521 were included and all reviewed for age, primary tumor size (PTS), laterality, receptor status like estrogen receptor (ER) progesterone receptor (PR) and Her-2-Neu receptor, presence or absence of BM with sites of involvement and time interval between diagnosis of BC and appearance of BM.

Breast carcinoma with asymptomatic metastasis to the gallbladder.

The biliary tract is an unusual site of metastasis from breast carcinoma, and this has rarely been reported in the literature. We report the case of a 42-year-old woman diagnosed with invasive lobular carcinoma of the breast who underwent laparoscopic cholecystectomy for an incidental finding of gallbladder wall thickening on ultrasonography, which was subsequently confirmed to be consistent with metastasis from the breast primary.

Infiltrating syringomatous adenoma of nipple.

Infiltrating syringomatous adenoma of the nipple is a rare, benign lesion with distinct clinical and histological features. Origin from ducts of dermal sweat glands has been postulated. Important differential diagnosis include nipple adenoma, tubular carcinoma and adenosquamous carcinoma.

Laparoscopic cholecystectomy in cirrhotic patients: feasibility in a developing country.

Background/aims: Although laparoscopic cholecystectomy (LC) has become the procedure of choice for cholelithiasis in the general population, many consider cirrhosis as a relative or absolute contraindication for laparoscopic surgery. The aim of this study was to confirm the safety of LC in cirrhotic patients in our set-up.

Materials And Methods: This is a retrospective case series including all the patients with cirrhosis who underwent LC for gallstones from January 2000 to December 2006 at our institution.

Complications of spilled gallstones during laparoscopic cholecystectomy: case series with review of literature.

The spillage of gallstones during laparoscopic cholecystectomy is a fairly common event, though, not documented and reported. These lost stones may have clinically important implications inclusive of added surgical procedures for their retrieval. We hereby address this issue and report 3 cases, with delayed consequences of these spilled gallstones.

Acute small bowel obstruction secondary to ileal endometrioma.

Pelvic endometriosis, a common disease of the female genital tract, may also affect the bowel, especially the rectosigmoid colon. Involvement of small intestine occurs very infrequently. A case of small bowel obstruction caused by ileal endometriosis is reported.