Merkel cell carcinoma: a forty-year experience at the Peter MacCallum Cancer Centre.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine skin malignancy, with Australia having the highest reported incidence in the world. There is currently a lack of consensus regarding optimal management of this disease. METHODS: This was a retrospective audit conducted by reviewing existing medical records of MCC patients presenting to the Peter MacCallum Cancer Centre (PMCC) between 1980 and 2018. The primary endpoint was locoregional recurrence. The secondary endpoints were distant recurrence, disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 533 patients were identified. Locoregional recurrence occurring at one, two and 5 years was 24, 31 and 32%, respectively. The estimated 5-year OS and DFS were 46% (95% Confidence Interval [CI] 41-51%) and 34% (95% CI 30-39%) respectively. Older age at diagnosis (hazard ratio [HR] per year = 1.07, 95% CI 1.06-1.07, p < 0.001), and larger primary tumour diameter (HR =1.16, 95% CI 1.03-1.31, p = 0.019) were associated with worse OS on multivariable analysis. Positive or negative histopathological margin status was not associated with OS or DFS differences in patients treated with post-operative radiotherapy. CONCLUSIONS: In our study, about a third of patients developed locoregional recurrence, distal recurrence or both, and there appears to be no change over the last four decades. If treated with adjuvant radiotherapy, there is no difference in OS or DFS with positive surgical margins. Findings should influence future guidelines.

The utilization of allied and community health services by cancer patients living in regional and remote geographical areas in Australia.

INTRODUCTION: Cancer patients in Australia's Northern Territory (NT) face unique challenges to accessing cancer-related community and allied health services (referred here as 'health services'). This is in part due to the NT's unique geographic, socioeconomic and demographic profile. This paper describes the use of health services by cancer patients in the NT. METHODS: Adult cancer patients attending appointments at a cancer centre in Darwin, NT and who were diagnosed within the past five years were invited to participate in face-to-face interviews about their use of allied and community health services. A descriptive analysis of health services utilization was conducted. RESULTS: Of the 76 participants interviewed, 63% identified as non-Indigenous, 53% female and 45% lived in very remote areas. Mean age at interview was 58.7 years (SD 13.2). Overall, 82% of participants utilized at least one health service since their cancer diagnosis. All Indigenous participants used at least one service, while 28% of non-Indigenous participants did not use any health service. The services most frequently used by participants were community services (42%) and information sources (40%). CONCLUSION: The findings from this study suggest there is variation in the type of community and allied health services used by NT cancer patients across clinical and demographic groups (including Indigenous status). Further qualitative enquiry is needed to better understand this variation, which may reflect differences in service preference, accessibility, health literacy of patients or patient engagement. Such knowledge may inform service delivery improvements to better support cancer patients through their cancer care pathway.

Treatment and outcomes for indigenous and non-indigenous lung cancer patients in the Top End of the Northern Territory.

BACKGROUND: Lung cancer is the most common cause of cancer-related mortality for both Indigenous and non-Indigenous Australians, and the death rate of lung cancer in Indigenous Australians is increasing. AIMS: To provide a comprehensive description of patterns of lung cancer presentation, diagnosis, treatment and outcomes in Indigenous and non-Indigenous Australians in the Top End of the Northern Territory. METHODS: Retrospective cohort study of adult patients with a new diagnosis of lung cancer in the Top End between January 2010 and December 2014. Unadjusted survival probabilities by indigenous status were calculated. The primary end-point was all-cause mortality. RESULTS: Despite receiving similar diagnostic procedures and treatment, Indigenous Australians with lung cancer have poorer 1- and 5-year survival (25.0% and 9.4% respectively), when compared to non-Indigenous Australians included in the study (42.0% and 16.2% respectively). Indigenous lung cancer patients were more likely to be female (51.6% of indigenous patients were female, compared to 30.5% non-indigenous), be current smokers (61.3% vs 36.9%), have more comorbidities (73.6% vs 52.7%, 24.2% vs 5.3% and 30.8% vs 14.2% for respiratory disease, renal insufficiency and diabetes mellitus respectively), and live in more socio-economically disadvantaged (66.7% vs 14.2%) and very remote areas (66.1% vs 6.8%). They were also more likely to die at home, compared to their non-indigenous counterparts (64.3% vs 26.7%). CONCLUSIONS: Indigenous patients from the Top End diagnosed with lung cancer were more likely to have poorer survival outcomes when compared to non-indigenous people. Potential reasons for the discrepancy in survival need to be addressed urgently.

Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.

Immunohistochemical investigation of cytokine expression levels as biomarkers in transrectal ultrasound-guided needle biopsy specimens of prostate adenocarcinoma.

Cytokines influence the biological behaviour of prostate cancer (PC) and may influence patient outcome and serve as useful prognostic biomarkers. The aim of the present study was to evaluate cytokine expression levels in prostatic needle biopsy specimens and the association with clinicopathological characteristics of patients with PC. A total of 18 patients with PC who underwent transrectal ultrasound (TRUS) guided prostate biopsy were included in the clinical study. These patients were naïve to radiotherapy (RT) or androgen deprivation therapy prior to TRUS biopsy and clinical follow up data was collected. Cytokine expression levels were analysed by using immunohistochemistry and Spearman's correlation test was used to determine the correlation between cytokine expression and clinicopathological characteristics. Expression levels of pro-inflammatory TNF-α and IL-6 decreased as Gleason score (GS) increased; however, a statistically significant difference was not detected. A statically significant correlation was observed between needle biopsy specimen and pre-RT plasma sample expression levels of pro-inflammatory TNF-α and IL-6 (P=0.01 and P=0.05, respectively) and anti-inflammatory TGF-ß1 (P=0.05). However, further studies are needed to confirm these results using a larger sample size to confirm the prognostic value of pro-inflammatory TNF-α and IL-6 and anti-inflammatory TGF-ß1 in patients with PC.

Do histopathological features of breast cancer in Australian Indigenous women explain the survival disparity? A two decade long study in the Northern Territory.

AIMS: In the Northern Territory (NT) of Australia, Indigenous women have a lower incidence of breast cancer, but a higher mortality than Non-indigenous women. The aim of this study was to describe and compare breast cancer pathological features related to stage and biological aggression between the two groups. METHODS: Subjects were identified by extract from the NT Cancer Registry in two separate cohorts, cohort 1 (1991-2000) and cohort 2 (2001-2010). Data from cohort 1 included age, stage, tumor grade and estrogen receptor status (ER) and treatment completion. Additional pathological variables including tumor size, HER2 status, lymphovascular invasion and derived tumor phenotype were available for cohort 2. Bivariate P values for categoric variables were calculated using Fisher's exact tests.  The Wilcoxon rank-sum test was used to compare cohort 2. Logistic regression was used to calculate odds ratios. RESULTS: There were 359 (44 indigenous) eligible women in cohort 1 and 526 (100 indigenous) for cohort 2. In cohort 1, in both cohorts, indigenous women were more likely to present at an advanced stage, but there was no difference in ER status or tumor grade. When derived phenotypes were compared, indigenous women were less likely to have better prognosis luminal A tumors, and more likely to have HER2-enriched tumors. CONCLUSION: This two decade long comparison of the pathological features of breast cancer between indigenous and nonindigenous women of the NT has confirmed that Indigenous women not only present at a later stage than NI women but are also afflicted by poorer prognosis tumors, particularly HER2 enriched.

Levels of plasma cytokine in patients undergoing neoadjuvant androgen deprivation therapy and external beam radiation therapy for adenocarcinoma of the prostate.

BACKGROUND: Radiotherapy (RT) alone or in combination with androgen deprivation therapy (ADT) is most common non-operative treatments for localised prostate cancer (PC). Some circulatory cytokines are believed to play an important role in RT resistance and lead to tumour progression, invasion, and angiogenesis. The aim of this study is to assess the influence of ADT and RT on the expression of circulatory cytokines levels in plasma at different time points. METHODS: Between Nov 2015 and Aug 2016, 18 patients with localized PC were selected for this clinical study. All patients had received neoadjuvant ADT using a leuteinizing hormone-releasing hormone (LH-RH) analogs prior to RT. Peripheral blood samples were collected prior to ADT, before RT, at the end of RT and 3 months after the completion of RT. Blood plasma samples were monitored for the pro-inflammatory and profibrotic cytokines TNF-α, TGF-ß1, IL-6, and IL-8, using enzyme-linked immunosorbent assay (ELISA) procedures. RESULTS: The concentration of TGF-ß1 rose while IL-6 levels declined in post-ADT samples when compared pre-ADT. Levels of TGF-ß1 increased in post-RT blood plasma compared to pre-RT blood plasma. Those changes were not statically significant. Three months post-RT completion, TGF-ß1 levels decreased and IL-6 and IL-8 levels increased. Although levels of TGF-ß1, IL-6 and IL-8 were found to be altered 3 months post-RT completion, only changes in IL-8 levels were found to be statistically significant (P=0.05). CONCLUSIONS: In conclusion the changes in cytokines levels have been found after ADT and RT, which strengthen the finding of other clinical studies. Accept that small numbers of samples made difficult to attain significant results. Large clinical studies will be required to validate these findings and hopefully become useful biomarkers in the clinical setting to predict patient outcome and success of treatment received.

Clinical, FDG-PET and molecular markers of immune checkpoint inhibitor response in patients with metastatic Merkel cell carcinoma.

BACKGROUND: Metastatic Merkel cell carcinoma (mMCC) is an aggressive neuroendocrine malignancy of the skin with a poor prognosis. Immune checkpoint inhibitors (ICIs) have shown substantial efficacy and favorable safety in clinical trials. METHODS: Medical records of patients (pts) with mMCC treated with ICIs from August 2015 to December 2018 at Peter MacCallum Cancer Centre in Australia were analyzed. Response was assessed with serial imaging, the majority with FDG-PET/CT scans. RNA sequencing and immunohistochemistry for PD-L1, CD3 and Merkel cell polyomavirus (MCPyV) on tumor samples was performed. RESULTS: 23 pts with mMCC were treated with ICIs. A median of 8 cycles (range 1 to 47) were administered, with treatment ongoing in 6 pts. Objective responses (OR) were observed in 14 pts (61%): 10 (44%) complete responses (CR) and 4 (17%) partial responses (PR). Median time to response was 8 weeks (range 6 to 12) and 12-month progression-free survival rate was 39%. Increased OR were seen in pts aged less than 75 (OR 80% vs 46%), no prior history of chemotherapy (OR 64% vs 50%), patients with an immune-related adverse event (OR 100% vs 43%) and in MCPyV-negative tumors (OR 69% vs 43%). Pts with a CR had lower mean metabolic tumor volume on baseline FDG-PET/CT scan (CR: 35.7 mL, no CR: 187.8 mL, p=0.05). There was no correlation between PD-L1 positivity and MCPyV status (p=0.764) or OR (p=0.245). 10 pts received radiation therapy (RT) during ICI: 4 pts started RT concurrently (OR 75%, CR 50%), 3 pts had isolated ICI-resistant lesions successfully treated with RT and 3 pts with multisite progression continued to progress despite RT. Overall, 6 pts (26%) had grade 1-2 immune-related adverse events. CONCLUSION: ICIs showed efficacy and safety in mMCC consistent with trial data. Clinical and imaging predictors of response were identified.

Cytokines expression levels from tissue, plasma or serum as promising clinical biomarkers in adenocarcinoma of the prostate: a systematic review of recent findings.

Prostate cancer (PC) is a common cancer (excluding non-melanoma skin cancer) in men in many parts of the world, although incidence and mortality rates vary significantly by population. In current medical practice, prognostic markers for PC include the presenting serum prostate-specific antigen (PSA) level, tumour Gleason score (GS) and clinical tumour stage. However, existing pre-treatment factors cannot be used to predict acute radiotherapy (RT)-induced toxicity. Therefore, new protein biomarkers are required in RT oncology to improve decision-making, treatment and therapy monitoring for PC patients. The aim of this systematic review is to the update potential research to address the difference in cytokine expression and their association with RT-induced toxicity and clinical outcomes. Studies were collected after searching three electronic databases: PubMed, Medline, and Google Scholar. An additional search was carried out through cross-check on a bibliography of selected articles. After the selection process made by two of the authors, 19 articles met the inclusion criteria and were included in the systematic review. Results from previous studies identified elevated levels of cytokines have been reported in several types of cancers and have sometimes correlated with disease progression or prognosis. Elevated levels of cytokine were noticed after immediate exposure to RT and their association with RT-induced acute/late toxicity of PC patients. Moreover, above studies also identified overexpression of cytokines on tumour biopsies and correlation with shortening cancer-specific survival and biochemical recurrence. Thus, altered levels of cytokine might be predictive biomarkers for RT-induced and clinical outcomes of PC patients.

Prognostic Role of MicroRNAs in Human Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: MicroRNAs (miRNAs) have been found to play an important role in the development and outcomes for multiple human cancers. Their role as a prognostic biomarker in non-small-cell lung cancer (NSCLC) remains unclear. This meta-analysis aims to clarify the role of various miRNAs in the survival of NSCLC patients. MATERIALS AND METHODS: All studies were identified through medical database search engines. A meta-analysis was conducted to assess the correlation between miRNAs expressions and overall survival among those NSCLC studies. Relevant data were extracted from each eligible study regarding baseline characteristics and key statistics such as hazard ratio (HR), 95% confidence interval (CI), and P value, which were utilized to calculate a pooled effect size. RESULT: Thirty-two studies were included in the meta-analysis. Using a random effect model, the combined HR and 95% CI for overall survival (OS) was calculated as 1.59 (1.39-1.82), predicting a poor overall survival. Five miRNAs (miR-21, miR-155, miR-let-7, miR-148a, and miR-148b) were found to be of significance for predicting OS in at least two studies, hence, selected for subgroup analysis. Subgroup analysis disclosed that elevated levels of miR-21 and miR-155 in both cancer tissue and blood samples were associated with worse OS. Compared to American studies (I-squared: <0.001% and P value: 0.94), Asian and European studies exhibited greater heterogeneity in miRNA expression and relationship to OS (I-squared, P values were approximately 78.85%, <0.001 and 61.28%, 0.006, respectively). These subgroup analyses also highlighted that elevated expression of miR-21 and miR-155 and low levels of expression of miR-148a, miR-148b, and miR-let-7 were associated with poor prognosis in NSCLC. CONCLUSION: miR-21, miR-155, miR-148a, miR-148b, and miR-let-7 are consistently up- or downregulated in NSCLC and are associated with poor OS. These miRNAs show potential as useful prognostic biomarkers in the diagnosis, treatment, and follow-up of NSCLC.

Development of quality indicators to monitor radiotherapy care for men with prostate cancer: A modified Delphi method.

BACKGROUND AND PURPOSE: Quality indicators (QIs) have been developed for many aspects of prostate cancer care, but are under-developed with regard to radiotherapy treatment. We aimed to develop a valid, relevant and feasible set of core QIs to measure quality of radiotherapy care in men with prostate cancer. MATERIALS AND METHODS: We used a RAND-modified Delphi process to select QIs that were regarded as both important and feasible measures of quality radiotherapy care. This involved two phases: (1) a literature review to identify a list of proposed QIs; and (2) a QI selection process by an expert panel (n = 12) conducted in a series of three rounds: two online questionnaires' and one face-to-face meeting. The RAND criterion identified variation in ratings and determined the level of agreement after each round of voting. RESULTS: A total of 144 candidate QIs, which included measures from pre-treatment to post-treatment and survivorship care were identified. After three rounds of voting, the panel approved a comprehensive set of 17 QIs, with most assessing a process of care (n = 16, 94.1%) and the remaining assessing a health outcome. CONCLUSION: This study developed a core set of 17 QIs which will be used to report from the Prostate Cancer Outcomes Registry-Australia & New Zealand, to monitor the quality of radiotherapy care prostate cancer patients receive.

Palliative chemoradiotherapy versus radiotherapy alone for dysphagia in advanced oesophageal cancer: a multicentre randomised controlled trial (TROG 03.01).

BACKGROUND: A short course of radiotherapy is commonly prescribed for palliative relief of malignant dysphagia in patients with incurable oesophageal cancer. We compared chemoradiotherapy with radiotherapy alone for dysphagia relief in the palliative setting. METHODS: This multicentre randomised controlled trial included patients with advanced or metastatic oesophageal cancer who were randomly assigned (1:1) through a computer-generated adaptive biased coin design to either palliative chemoradiotherapy or radiotherapy alone for treatment of malignant dysphagia at 22 hospitals in Australia, Canada, New Zealand, and the UK. Eligible patients had biopsy-proven oesophageal cancer that was unsuitable for curative treatment, symptomatic dysphagia, Eastern Cooperative Oncology Group performance status 0-2, and adequate haematological and renal function. Patients were stratified by hospital, dysphagia score (Mellow scale 1-4), and presence of metastases. The radiotherapy dose was 35 Gy in 15 fractions over 3 weeks for patients in Australia and New Zealand and 30 Gy in ten fractions over 2 weeks for patients in Canada and the UK. Chemotherapy consisted of one cycle of intravenous cisplatin (either 80 mg/m2 on day 1 or 20 mg/m2 per day on days 1-4 of radiotherapy at clinician's discretion) and intravenous fluorouracil 800 mg/m2 per day on days 1-4 of radiotherapy in week 1. Patients were assessed weekly during treatment. The primary endpoint was dysphagia relief (defined as ≥1 point reduction on the Mellow scale at 9 weeks and maintained 4 weeks later), and key secondary endpoints were dysphagia progression-free survival (defined as a worsening of at least 1 point on the Mellow scale from baseline or best response) and overall survival. These endpoints were analysed in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00193882. This trial is closed. FINDINGS: Between July 7, 2003, and March 21, 2012, 111 patients were randomly assigned to chemoradiotherapy and 109 patients to radiotherapy. One patient in the chemoradiotherapy group was omitted from analysis because of ineligibility. 50 (45%, 95% CI 36-55) patients in the chemoradiotherapy group and 38 (35%, 26-44) in the radiotherapy group obtained dysphagia relief (difference 10·6%, 95% CI -2 to 23; p=0·13). Median dysphagia progression-free survival was 4·1 months (95% CI 3·5-4·8) versus 3·4 months (3·1-4·3) in the chemoradiotherapy and radiotherapy groups, respectively (p=0·58), and median overall survival was 6·9 months (95% CI 5·1-8·3) versus 6·7 months (4·9-8·0), respectively (p=0·88). Of the 211 patients who commenced radiotherapy, grade 3-4 acute toxicity occurred in 38 (36%) patients in the chemoradiotherapy group and in 17 (16%) patients in the radiotherapy group (p=0·0017). Anaemia, thrombocytopenia, neutropenia, oesophagitis, diarrhoea, nausea and vomiting, and mucositis were significantly worse in patients who had chemoradiotherapy than in patients who had radiotherapy. INTERPRETATION: Palliative chemoradiotherapy showed a modest, but not statistically significant, increase in dysphagia relief compared with radiotherapy alone, with minimal improvement in dysphagia progression-free survival and overall survival with chemoradiotherapy but at a cost of increased toxicity. A short course of radiotherapy alone should be considered a safe and well tolerated treatment for malignant dysphagia in the palliative setting. FUNDING: National Health and Medical Research Council, Canadian Cancer Society Research Institute, Canadian Cancer Trials Group, Trans Tasman Radiation Oncology Group, and Cancer Australia.

Development of Indicators to Assess Quality of Care for Prostate Cancer.

BACKGROUND: The development, monitoring, and reporting of indicator measures that describe standard of care provide the gold standard for assessing quality of care and patient outcomes. Although indicator measures have been reported, little evidence of their use in measuring and benchmarking performance is available. A standard set, defining numerator, denominator, and risk adjustments, will enable global benchmarking of quality of care. OBJECTIVE: To develop a set of indicators to enable assessment and reporting of quality of care for men with localised prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: Candidate indicators were identified from the literature. An international panel was invited to participate in a modified Delphi process. Teleconferences were held before and after each voting round to provide instruction and to review results. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Panellists were asked to rate each proposed indicator on a Likert scale of 1-9 in a two-round iterative process. Calculations required to report on the endorsed indicators were evaluated and modified to reflect the data capture of the Prostate Cancer Outcomes Registry-Australia and New Zealand (PCOR-ANZ). RESULTS AND LIMITATIONS: A total of 97 candidate indicators were identified, of which 12 were endorsed. The set includes indicators covering pre-, intra-, and post-treatment of PCa care, within the limits of the data captured by PCOR-ANZ. CONCLUSIONS: The 12 endorsed quality measures enable international benchmarking on the quality of care of men with localised PCa. Reporting on these indicators enhances safety and efficacy of treatment, reduces variation in care, and can improve patient outcomes. PATIENT SUMMARY: PCa has the highest incidence of all cancers in men. Early diagnosis and relatively high survival rates mean issues of quality of care and best possible health outcomes for patients are important. This paper identifies 12 important measurable quality indicators in PCa care.

Cytochrome P450 Allele CYP3A7*1C Associates with Adverse Outcomes in Chronic Lymphocytic Leukemia, Breast, and Lung Cancer.

CYP3A enzymes metabolize endogenous hormones and chemotherapeutic agents used to treat cancer, thereby potentially affecting drug effectiveness. Here, we refined the genetic basis underlying the functional effects of a CYP3A haplotype on urinary estrone glucuronide (E1G) levels and tested for an association between CYP3A genotype and outcome in patients with chronic lymphocytic leukemia (CLL), breast, or lung cancers. The most significantly associated SNP was rs45446698, an SNP that tags the CYP3A7*1C allele; this SNP was associated with a 54% decrease in urinary E1G levels. Genotyping this SNP in 1,008 breast cancer, 1,128 lung cancer, and 347 CLL patients, we found that rs45446698 was associated with breast cancer mortality (HR, 1.74; P = 0.03), all-cause mortality in lung cancer patients (HR, 1.43; P = 0.009), and CLL progression (HR, 1.62; P = 0.03). We also found borderline evidence of a statistical interaction between the CYP3A7*1C allele, treatment of patients with a cytotoxic agent that is a CYP3A substrate, and clinical outcome (Pinteraction = 0.06). The CYP3A7*1C allele, which results in adult expression of the fetal CYP3A7 gene, is likely to be the functional allele influencing levels of circulating endogenous sex hormones and outcome in these various malignancies. Further studies confirming these associations and determining the mechanism by which CYP3A7*1C influences outcome are required. One possibility is that standard chemotherapy regimens that include CYP3A substrates may not be optimal for the approximately 8% of cancer patients who are CYP3A7*1C carriers.

Post-traumatic stress disorder and post-traumatic growth in breast cancer patients--a systematic review.

Breast cancer (BC) is potentially a traumatic stressor which may be associated with negative outcomes, such as post-traumatic stress disorder (PTSD) or positive changes, such as post-traumatic growth (PTG). This study aims to identify the core issues of BC related PTSD, PTG and psychological distress by interrogating the literature in BC survivors. We have also highlighted issues related to the assessment, diagnosis and clinical management of PTSD and PTG. The authors systematically reviewed studies published from 1985 to 2014 pertaining to PTSD, psychological distress and PTG in BC survivors with particular attention paid to incidence rates and causative factors. Multiple studies intimated that women with BC have evidence of PTSD at the initial stages of diagnosis, whereas PTG develops once patients undergo treatment. Early diagnosis and treatment of PTSD/PTG is paramount from literature review but the previously mentioned relationship between PTSD and PTG in BC patients could not be verified. It is evident from the literature that a small percentage of BC patients experience PTSD, while the majority experience PTG after BC diagnosis and treatment. Future research should include prospective studies focusing on high-risk patients, causative factors and the development of psychological interventions.