Differential Chemotherapeutic Sensitivity for Breast Tumors With “BRCAness”: A Review

BRCA1 or BRCA2 mutations predispose to cancer development, primarily through their loss of role in the repair of DNA double‐strand breaks. They play a key role in homologous recombination repair, which is a conservative, error‐free DNA repair mechanism. When mutated, other alternative, error‐prone mechanisms for DNA repair take over, leading to genomic instability. Somatic mutations are rare in sporadic breast tumors, but expression of BRCA1 and BRCA2 genes can be downregulated in other mechanistic ways. These tumors have similar features in terms of their phenotypic and genotypic profiles, which are normally regulated by these genes, and mutations lead to defective DNA repair capacity, called “BRCAness.” Attempts have been made to exploit this differentially expressed feature between tumors and normal tissues by treatment with DNA‐damaging chemotherapy agents. Cells with this functional BRCA deficiency should be selectively susceptible to DNA‐damaging drugs. Preclinical and early clinical (primarily retrospective) evidence supports this approach. In contrast, there is emerging evidence of relative resistance of tumors containing BRCA1 or BRCA2 mutations (or BRCAness) to taxanes. In this review, we summarize the data supporting differential chemotherapeutic sensitivity on the basis of defective DNA repair. If confirmed with available, clinically applicable techniques, this differential chemosensitivity could lead to treatment choices in breast cancer that have a more individualized biologic basis.     

Erratum to Slattery et al. “Dietary calcium,vitamin D,VDR genotypes and colorectal cancer.” Int J Cancer 2004;111:750–757

The original article to which this Erratum refers was published in International Journal of Cancer (2004) 111(5) 750–757 DOI: 10.1002/ijc.20330     

Exploratory thoracotomy on a patient with previous malignancy—“metastasis” or “new primary” or “unrelated lesion”

Surgical resection of a solitary pulmonary metastasis is an established procedure. A medical generation ago when such a shadow appeared on chest roentgenogram of a patient who had known cancer elsewhere in body, it was assumed to be “metastasis” from an extrathoracic site. With increasing advances in knowledge, the occurrence of second primary or new lesion is now no more curiosity in clinical practice. To one's surprise, the lesions that are assumed to be metastatic have often turned out to be “fresh” lesion or even unrelated benign, granulomatous, inflammatory, or parasitic lesion. This paper analyses 66 patients during a period of 20 years who underwent thoracotomy for such solitary pulmonary lesions, and emphasizes the role of diagnostic-cum-therapeutic-thoracotomy in such a clinical situation where in prethoracotomy tissue diagnosis is not forthcoming.     

“Early” tongue carcinoma

This is a retrospective study done in 89 patients who were treated for stage I lingual carcinoma, to determine the local control and 5-year salvage rate and the site and frequency of recurrences with salvage rate with a second modality.     

Does “Black” Brain Mean Doom? Computed Tomography in the Prediction of Outcome in Children with Severe Head Injuries: “Benign” vs “Malignant” Brain Swelling

A retrospective review of initial and subsequent CT scans of 179 children who has suffered severe head injury requiring admission to intensive care was performed. The aim was to define the CT appearance which was always associated with a poor outcome. The children whose brain showed poor definition of basal ganglia and grey-white differentiation overall, together with sufficient swelling to obliterate the ambient cistern and third ventricle always died or remained in a vegetative state. Over half of these had reduced brain density, and several had small focal high densities consistent with contusions or petechial haemorrhages. A typical appearance showed homogeneous scans at the levels of the ambient cistern and thalami with no normal internal brain detail. Conversely obliteration of the ambient cistern associated with a large surface collection was compatible with complete recovery if grey-white definition remained normal and treatment was prompt.