Nucleosome reorganisation in breast cancer tissues.

BACKGROUND: Nucleosome repositioning in cancer is believed to cause many changes in genome organisation and gene expression. Understanding these changes is important to elucidate fundamental aspects of cancer. It is also important for medical diagnostics based on cell-free DNA (cfDNA), which originates from genomic DNA regions protected from digestion by nucleosomes. RESULTS: We have generated high-resolution nucleosome maps in paired tumour and normal tissues from the same breast cancer patients using MNase-assisted histone H3 ChIP-seq and compared them with the corresponding cfDNA from blood plasma. This analysis has detected single-nucleosome repositioning at key regulatory regions in a patient-specific manner and common cancer-specific patterns across patients. The nucleosomes gained in tumour versus normal tissue were particularly informative of cancer pathways, with ~ 20-fold enrichment at CpG islands, a large fraction of which marked promoters of genes encoding DNA-binding proteins. The tumour tissues were characterised by a 5-10 bp decrease in the average distance between nucleosomes (nucleosome repeat length, NRL), which is qualitatively similar to the differences between pluripotent and differentiated cells. This effect was correlated with gene activity, differential DNA methylation and changes in local occupancy of linker histone variants H1.4 and H1X. CONCLUSIONS: Our study offers a novel resource of high-resolution nucleosome maps in breast cancer patients and reports for the first time the effect of systematic decrease of NRL in paired tumour versus normal breast tissues from the same patient. Our findings provide a new mechanistic understanding of nucleosome repositioning in tumour tissues that can be valuable for patient diagnostics, stratification and monitoring.

Avoiding breast cancer surgery in a select cohort of complete responders to neoadjuvant chemotherapy: The long-term outcomes.

BACKGROUND: Lately, there has been a resurgence of interest in de-escalation of breast surgery in complete responders to neoadjuvant chemotherapy (NAC). Advanced cytotoxic & targeted therapies have improved tumour response.This study evaluates long-term outcomes of post-NAC breast cancer patients, in relation to their surgical management dictated by the NAC response. MATERIALS AND METHODS: Post-NAC breast cancer patients from January 2000 to December 2010 were divided into "No surgery", "WLE" and "Mastectomy" groups. ANOVA and Kaplan-Meier statistical analyses were used to compare overall survival (OS) and disease-free-survival (DFS) in these groups. RESULTS: This retrospective study included 121 patients with a long median follow-up of 11.5 years. At 10 years the OS was 66.10% and DFS was 59.82%. Complete NAC-responders did not undergo breast surgery but received radiotherapy. Patients were divided into No surgery (n = 28), WLE (n = 44), Mastectomy (n = 49) groups.Comparisons of OS and DFS between groups showed statistically significant differences (p = 0.0003, p = 0.0007 respectively). The no surgery group showed low local recurrence (7.14%). CONCLUSION: The observed slightly better long-term outcomes with low local recurrences in complete NAC-responders who did not undergo breast surgery but received radiotherapy could be linked to cautious response assessment and meticulous patient selection with early, biologically favourable breast cancer.Importance of PCR assessment cannot be underestimated if breast surgery were to be de-escalated or even omitted in complete NAC-responders.Considering the study limitations, avoiding surgery in all complete NAC-responders may still not be the preferred option. Future appropriate clinical trials with well-defined protocols may pave the way forward.

Single stage immediate breast reconstruction with acellular dermal matrix and implant: Defining the risks and outcomes of post-mastectomy radiotherapy.

INTRODUCTION: The objective of this study is to evaluate outcomes and complications in patients with single-stage ADM-implant based immediate breast reconstruction with and without radiotherapy (RT), highlighting the effects of RT on the reconstruction. MATERIALS AND METHODS: This prospective study recruited 91 consecutive patients who underwent skin-sparing, nipple-sparing or wise-pattern skin reduction mastectomy with direct-to-implant breast reconstruction with ADMs using sub-pectoral or pre-pectoral approach at the two breast units. Early and late complications like seroma, delayed wound healing, wound breakdown, infection, capsular contracture, implant loss and revision surgery were evaluated in the RT and non-RT groups. RESULTS: In the total cohort of 91 patients, 29 received adjuvant RT and 62 did not need RT. In the RT group, 3-7% of them had early complications like seroma, wound infections and delayed healing. 20.7% had post-RT capsular contractures which either required revision surgery with autologous flap (6.9%) or capsulotomy with exchange of implant (6.9%). In the non-RT group, 7-9% cases had seroma & wound infections, 3.06% had delayed wound healing and 7.25% had capsular contracture. 13.04% required revision surgery due to infection, implant loss or failure to achieve expectations. The total loss of implants in the cohort was 7.14% (RT group 6.9% and non-RT group 7.25%). The need for PMRT could have been predicted pre-operatively in the RT group in 55.17% cases based on the extent of disease, multifocality, tumour grade and positive LN status on imaging. CONCLUSION: ADM based reconstruction in patients anticipated to receive adjuvant RT is always debatable. Though there is no significant difference in the revision surgeries in our study of the 2 groups, the rate of capsular contracture as expected, was higher in the RT group. Hence, pre-operative discussion on the need for RT highlighting the risks and complications will help patients make a better-informed choice.

Remote cutaneous breast carcinoma metastasis mimicking dermatitis.

Cutaneous metastases from primary internal malignancies are an uncommon presentation. Cutaneous metastases are more frequently seen in breast cancer than in any other visceral malignancy in women. Medical practitioners should be vigilant of the possibility of unusual presentations of metastatic disease in breast cancer patients with lobular carcinoma presenting as cutaneous lesions mimicking benign dermatological conditions. Herein, we present a case of a 75-year-old woman presenting with cutaneous lobular breast carcinoma metastases on her anterior right leg, which had previously been misdiagnosed as dermatitis for 9 years.