Comparison of the Nottingham Prognostic Index and OncotypeDX© recurrence score in predicting outcome in estrogen receptor positive breast cancer

IntroductionTraditionally, Nottingham prognostic index (NPI) informed prognosis in patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, node negative (ER+/HER2-/LN-) breast cancer. At present, OncotypeDX© Recurrence Score (RS) predicts prognosis and response to adjuvant chemotherapy (AC).AimsTo compare NPI and RS for estimating prognosis in ER + breast cancer.MethodsConsecutive patients with ER+/HER2-/LN- disease were included. Disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier and Cox regression analyses.Results1471 patients met inclusion criteria. The mean follow-up was 110.7months. NPI was calculable for 1382 patients: 19.8% had NPI≤2.4 (291/1471), 33.0% had NPI 2.41–3.4 (486/1471), 30.0% had NPI 3.41–4.4 (441/1471), 10.9% had NPI 4.41–5.4 (160/1471), and 0.3% had NPI>5.4 (4/1471). In total, 329 patients underwent RS (mean RS: 18.7) and 82.1% had RS < 25 (270/329) and 17.9% had RS ≥ 25 (59/329). Using multivariable Cox regression analyses (n = 1382), NPI independently predicted DFS (Hazard ratio (HR): 1.357, 95% confidence interval (CI): 1.140–1.616, P < 0.001) and OS (HR: 1.003, 95% CI: 1.001–1.006, P = 0.024). When performing a focused analysis of those who underwent both NPI and RS (n = 329), neither biomarker predicted DFS or OS. Using Kaplan Meier analyses, NPI category predicted DFS (P = 0.008) and (P = 0.026) OS. Conversely, 21-gene RS group failed to predict DFS (P = 0.187) and OS (P = 0.296).ConclusionIn our focused analysis, neither NPI nor RS predicted survival outcomes. However, in the entire series, NPI independently predicted both DFS and OS. On the 40th anniversary since its derivation, NPI continues to provide accurate prognostication in breast cancer, outperforming RS in the current study.     

Towards the intra-operative use of Raman spectroscopy in breast cancer—overcoming the effects of theatre lighting

The ability to use Raman spectroscopy to assess tissue in the operative theatre setting could be advantageous for both patients and clinicians. In this study, a method of overcoming the deleterious effects of theatre lighting on the Raman spectra is demonstrated. The effectiveness of this technique is highlighted both within the theatre setting and using human lymph node tissue. The portable MiniRam II Raman spectroscopy device that incorporated a 785-nm laser was used in all experiments. This is an important step towards the use of Raman spectroscopy as a means of analysing sentinel lymph nodes in patients who have been newly diagnosed with breast cancer.     

Diet and Bladder Cancer: A Case–Control Study

To investigate possible relationships between diet and risk for bladder cancer in Serbia, the hospital-based case–control study was carried out. This study included 130 newly diagnosed bladder cancer patients and the same number of controls matched by sex, age (%±%2 years) and type of residence (rural or urban). Dietary information was obtained by using a food frequency questionnaire. Initial case–control comparisons were based on tertiles of average daily intake of control group. The odds ratios (ORs) were computed for each tertile, with the lowest tertile defined as the referent category. All variables (food items) significantly related to bladder cancer were included in multivariable logistic regression analysis. According to this analysis, risk factors for bladder cancer appeared to be consumption of liver (OR=6.60, 95%CI=1.89–23.03), eggs (OR=3.12, 95%CI=1.10–8.80), pork (OR=2.99, 95%CI=1.16–7.72), and pickled vegetable (OR=3.25, 95%CI=1.36–7.71). A protective effect was found for dietary intake of kale (OR=0.21, 95%CI=0.06–0.73), cereals (OR=0.19, 95%CI=0.06–0.62), tangerines (OR=0.21, 95%CI=0.07–0.68), cabbage (OR=0.27, 95% CI=0.11–0.68), and carrots (OR=0.15, 95%CI=0.05–0.41). The study indicated a potentially important role for dietary fat and pickled vegetables in bladder carcinogenesis. An inverse association was recorded between consumption of fruits, vegetables and cereals, and the development of bladder cancer.     

Long-Term Risk of Osteoporotic Fracture in Malmö

The objectives of the present study were to estimate long-term risks of osteoporotic fractures. The incidence of hip, distal forearm, proximal humerus and vertebral fracture were obtained from patient records in Malmo¨, Sweden. Vertebral fractures were confined to those coming to clinical attention, either as an inpatient or an outpatient case. Patient records were examined to exclude individuals with prior fractures at the same site. Future mortality rates were computed for each year of age from Poisson models using the Swedish Patient Register and the Statistical Year Book. The incidence and lifetime risk of any fracture were determined from the proportion of individuals fracture-free from the age of 45 years. Lifetime risk of shoulder, forearm, hip and spine fracture were 13.3%, 21.5%, 23.3% and 15.4% respectively in women at the age of 45 years. Corresponding values for men at the age of 45 years were 4.4%, 5.2%, 11.2% and 8.6%. The risk of any of these fractures was 47.3% and 23.8% in women and men respectively. Remaining lifetime risk was stable with age for hip fracture, but decreased by 20–30% by the age of 70 years in the case of other fractures. Ten and 15 year risks for all types of fractures increased with age until the age of 80 years, when they approached lifetime risks because of the competing probabilities of fracture and death. We conclude that fractures of the hip and spine carry higher risks than fractures at other sites, and that lifetime risks of fracture of the hip in particular have been underestimated. Received: 9 November 1999 / Accepted: 2 February 2000     

Instability of the hip in neonates. An ethnic and geographical study in 24,101 newborn infants in Malmö

In a prospective study conducted between 1990 and 1997, 24 101 newborn infants were examined for neonatal instability of the hip and classified by the ethnic origin of their parents. In 63% their mother and father were of Swedish extraction and in 24% they were born in a foreign country. Those of foreign extraction were split into ethnic and geographical subgroups. Although the incidence of treated (dislocatable-unstable) hips was greater in Swedes (7.6/thousand), than in other geographical groups (5.8/thousand) it was not significantly different (p = 0.065). A total of 12.7/thousand were referred from the neonatal ward to the orthopaedic clinic with suspected dislocatable or unstable hips; 6.8/thousand were treated (5.4/thousand dislocatable, 1.4/thousand unstable), but 5.9/thousand were not treated since their ultrasound examination was normal. Two hips were diagnosed late and one case of mild avascular necrosis was found. Examination by dynamic ultrasound decreased the number of treated cases by 5.9/thousand but was not an absolute guarantee of diagnosis.     

Does oncotype DX recurrence score affect the management of patients with early-stage breast cancer?

BACKGROUND: Oncotype DX is a 21-gene assay that calculates a risk of distant recurrence in women with estrogen-receptor-positive, lymph node-negative breast cancer. The purpose of this study was to determine whether the results of Oncotype DX influence the decision to administer chemotherapy. METHODS: A retrospective study was performed on 85 consecutive patients with estrogen-receptor-positive, lymph node-negative breast cancer who had an Oncotype DX recurrence score (RS) obtained. Tumor size, tumor grade, and treatment were then compared within each risk category. Statistical analysis was performed using STATA software. RESULTS: Tumors that were high grade and Her-2/neu positive more frequently had a high RS. Treatment was changed as a result of Oncotype DX in 44% of patients. CONCLUSIONS: Oncotype DX RS is significantly related to tumor grade and Her2/neu status. In this study, the treatment of 44% of patients was altered as a consequence of Oncotype DX RS.     

Study on the prevalence of benlgn prostatic hyperplasia and prostatic cancer in China

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Columnar cell lesions of the breast: the missing link in breast cancer progression? A morphological and molecular analysis

Columnar cell lesions (CCLs) of the breast are a spectrum of lesions that have posed difficulties to pathologists for many years, prompting discussion concerning their biologic and clinical significance. We present a study of CCL in context with hyperplasia of usual type (HUT) and the more advanced lesions ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. A total of 81 lesions from 18 patients were subjected to a comprehensive morphologic review based upon a modified version of Schnitt's classification system for CCL, immunophenotypic analysis (estrogen receptor [ER], progesterone receptor [PgR], Her2/neu, cytokeratin 5/6 [CK5/6], cytokeratin 14 [CK14], E-cadherin, p53) and for the first time, a whole genome molecular analysis by comparative genomic hybridization. Multiple CCLs from 3 patients were studied in particular detail, with topographic information and/or showing a morphologic spectrum of CCL within individual terminal duct lobular units. CCLs were ER and PgR positive, CK5/6 and CK14 negative, exhibit low numbers of genetic alterations and recurrent 16q loss, features that are similar to those of low grade in situ and invasive carcinoma. The molecular genetic profiles closely reflect the degree of proliferation and atypia in CCL, indicating some of these lesions represent both a morphologic and molecular continuum. In addition, overlapping chromosomal alterations between CCL and more advanced lesions within individual terminal duct lobular units suggest a commonality in molecular evolution. These data further support the hypothesis that CCLs are a nonobligate, intermediary step in the development of some forms of low grade in situ and invasive carcinoma.     

Does the use of pretreatment MRI change the management of patients with newly diagnosed breast cancer?

Breast MRI plays a critical role in the diagnosis and management of breast cancer. The purpose of this study is to evaluate the effect of preoperative breast MRI on the management of a large cohort of breast cancer patients at our institution. This study is a retrospective chart review of all newly diagnosed breast cancer patients who underwent preoperative breast MRI at our institution between January 1, 2004 and December 31, 2009. 1352 patients comprised the study population. 241 (17.8%) patients underwent a change in surgical management as a result of preoperative MRI. Patients with tumors in the lower inner quadrant and the central breast and those with pathology of invasive lobular carcinoma were significantly more likely to have their management changed by preoperative MRI. There was also a significant trend for larger tumors to be associated with a change in surgical management. No statistically significant association was found between breast density and change in management. This study supports the recommendation for the use of preoperative breast MRI in the majority of newly diagnosed breast cancer patients, especially those with larger tumors, pathology of invasive lobular carcinoma, and tumors in the lower inner quadrant. Preoperative breast MRI is a useful tool for the evaluation of additional disease that led to a change in the surgical management of 17.8% of patients.     

Will the experience with tamoxifen in breast cancer help define the role of antiandrogens in prostate cancer?

Breast and prostate cancers are the two predominant hormone-responsive tumours. The use of the antioestrogen tamoxifen in the treatment of breast cancer has evolved over the past 30 y from treatment for advanced breast cancer to prevention. Tamoxifen is currently the endocrine treatment of choice for advanced breast cancer and for adjuvant therapy in a broad spectrum of women whose primary tumours have functional oestrogen receptors. It has also been shown to reduce the incidence of breast cancer in high-risk women. Non-steroidal antiandrogen therapy is used in the treatment of prostate cancer, but its role is still being defined. The clinical development of tamoxifen and that of the antiandrogens are reviewed and parallels are uncovered which provide insight into contemporary and future management of hormone-responsive prostate cancer.Prostate Cancer and Prostatic Diseases (2001) 4, 72-80     

Are risk factors for breast cancer similar in women with inflammatory breast cancer and in those with non-inflammatory breast cancer?

PURPOSE: The aim of the study was to compare reproductive factors in patients with inflammatory breast cancer (IBC), and with non-inflammatory breast cancer (non-IBC). The study was performed in two centers: one French including 49 IBC patients and 140 non-IBC and another Tunisian including 97 IBC and 139 non-IBC. Unconditional logistic regression was used for the analyses. PATIENTS AND METHODS: The French IBC patients had a lower educational level, a higher body mass index and a longer cumulative duration of breast-feeding, and they included a greater proportion of non-European women, than the non-IBC patients. In the multivariate analysis, only breast-feeding duration remained associated with the IBC status (P=10(-3)). These results could not be verified in the Tunisian series, because the duration of breast-feeding was unavailable in this center. RESULTS: This study suggests that the etiology of IBC might be different of that of non-IBC.     

Subclavicular recurrence of breast cancer: Does surgery play a role?

Occasionally, breast cancer relapses in the subclavicular region. In patients with failed multimodal treatment, or in those who develop an isolated recurrence, surgical resection may be useful to remove all macroscopically evident diseases. However, the procedure may be technically demanding and there are no published data regarding its benefits. The aim of the present study was to evaluate the feasibility and safety of subclavicular resection in breast cancer and provide indications as to whether it can contribute to disease control. We used a transpectoral approach to surgically remove isolated breast cancer recurrence in the subclavicular region in seven consecutive patients presenting over 2 years; in the eighth case a transmanubrial approach was necessary. We found that the surgical approach proposed is feasible and safe, with a 75% rate of complete resection; however, the series was characterised by a high rate of local and distant relapse. We conclude that the technique may be useful, in selected cases, for palliation only.     

Expression and clinical significance of FPARγ and β-catenin in breast cancer

Objective To study the expression of peroxisome proliferator-activated receptor γ (PPARγ) and β-catenin in breast cancer, and their correlations with clinicopathological parameters and prognosis. Methods Tissue samples obtained from 70 patients with breast cancer and 20 patients with breast benign mass were immunohistochemically examined for the expression of PPARγ and p-catenin. Results Overexpression rate of PPARγ protein was 34. 3% in breast cancer, significantly lower than that in breast benign mass. Abnormal expression rate of β-catenin in breast cancer was 67. 1%. A significant negative-correlation was found between the expression of PPARγ and β-catenin (r=-0. 398,P<0.05 ). PPARγ expression was inversely associated with histologic grade, tumor size, axillary lymph node metastasis,TNM stage and Ki-67 expression (P<0. 05), while positively correlated with ER status and overall survival rate (P<0. 05). Abnormal β-catenin expression was positively associated with histologic grade, axillary lymph node metastasis and TNM stage (P<0. 05), while inversely correlated with overall survival rate (P<0.05). Conclusion PPARγ and β-catenin are correlated with development of breast carcinoma,suggesting that detection of PPARγ and β-catenin may be of value in evaluating the biological behaviors and the prognosis of breast cancer.     

Neuroendocrine breast tumours: Breast cancer or neuroendocrine cancer presenting in the breast?

Neuroendocrine tumours (NET) of the breast are rare. Diagnosis depends on close scrutiny of core- or excisional-biopsy specimens for characteristic growth patterns (papillary, nesting or mixed), which should trigger immunohistochemical staining for neuroendocrine markers (in particular chromogranin and synaptophysin). The diagnosis is confirmed if a) >50% of the tissue specimen demonstrate neuroendocrine markers and b) in-situ ductal carcinoma is identified and/or imaging modalities exclude extra-mammary sites. Our literature search including the non-English literature identified 66 articles with data on 123 cases, including our own. Oestrogen receptors are not diagnostic for NET's of the breast as they are found in tumours of non-mammary origin, too. Half of reported cases of neuroendocrine tumours have axillary lymph node involvement. Breast-conserving surgery (wide local excision ± axillary clearance) is commonly performed for suitable tumours. Chemotherapy regimens utilised are commonly either platinum- (as for small-cell cancers) or anthracycline-based (as for primary breast cancers). Best management remains unknown.     

Expression and clinical significance of FPARγ and β-catenin in breast cancer

Objective To study the expression of peroxisome proliferator-activated receptor γ (PPARγ) and β-catenin in breast cancer, and their correlations with clinicopathological parameters and prognosis. Methods Tissue samples obtained from 70 patients with breast cancer and 20 patients with breast benign mass were immunohistochemically examined for the expression of PPARγ and p-catenin. Results Overexpression rate of PPARγ protein was 34. 3% in breast cancer, significantly lower than that in breast benign mass. Abnormal expression rate of β-catenin in breast cancer was 67. 1%. A significant negative-correlation was found between the expression of PPARγ and β-catenin (r=-0. 398,P<0.05 ). PPARγ expression was inversely associated with histologic grade, tumor size, axillary lymph node metastasis,TNM stage and Ki-67 expression (P<0. 05), while positively correlated with ER status and overall survival rate (P<0. 05). Abnormal β-catenin expression was positively associated with histologic grade, axillary lymph node metastasis and TNM stage (P<0. 05), while inversely correlated with overall survival rate (P<0.05). Conclusion PPARγ and β-catenin are correlated with development of breast carcinoma,suggesting that detection of PPARγ and β-catenin may be of value in evaluating the biological behaviors and the prognosis of breast cancer.     

Is a breast MRI possible and indicated in case of suspicion of breast cancer during lactation?

The paper tries to answer two questions: the safety of the injection of gadolinium during breastfeeding; the value of a breast MRI in the nursing mother if breast cancer is suspected. Recent Anglo-Saxon publications are in favour of continued breastfeeding following the injection of gadolinium. In fact, only a minute quantity of contrast product passes into the mother's milk, much less than the threshold recommended in paediatrics in the infant. However, a suspension of lactation for 24 h after the injection of gadolinium chelate is still recommended in France. The literature is poor as regards the contribution of the MRI during lactation, although the data indicates that the MRI is contributory, in spite of the physiological changes in the breast during this period. In fact, all of the lesions have been visualised and correctly classified according to the BI-RADS classification by the ACR¹. However, the semiology is specific and has to be known.     

Do racial disparities exist in the use of prostate cancer screening and detection tools in veterans?

ObjectiveTo determine whether racial disparities exist in the use of prostate cancer screening and detection tools in veterans.Methods and materialsAdministrative data were obtained from the Corporate Data Warehouse on a national cohort of 275,831 veterans (21% African American [AA]) between the ages of 40 and 70 years who were free of heart disease, did not have an elevated prostate specific antigen (PSA) level (>4 ng/ml), did not have other clinical signs of prostate cancer, had not been diagnosed with prostate cancer, and had not received treatment for prostate cancer between January 10, 1998 and September 30, 2000. Subjects were followed up until September 30, 2007. Regular users were defined as those with at least 1 annual visit to the Veterans Healthcare Administration (VHA) between October 1, 1998 and September 30, 2000. We sought to determine if race was significantly associated with PSA testing, the time to elevated PSA detection, the time to prostate biopsy, and the time to diagnosis of prostate cancer. Chi-square tests, logistic regression, and Cox proportional hazard models were used to test for associations between race and prostate cancer variables.ResultsEighty-four percent of the veterans between the ages 40 and 70 years undergo PSA testing. AA veterans are as likely as white veterans to undergo PSA testing. Screened AA veterans are more likely to have a PSA>4 ng/ml, undergo prostate biopsy, and be diagnosed with prostate cancer than screened white veterans. The time intervals between undergoing a prostate biopsy and being diagnosed with prostate cancer were statistically significantly shorter (although unlikely of clinical significance) for AA veterans with a PSA level>4 ng/ml than that for white veterans with a PSA level>4 ng/ml. When routine care in regular VHA users was compared with that of participants in major screening trials such as Prostate, Lung, Ovarian and Colon Cancer Trial and European Study of Screening for Prostate Cancer, prostate biopsy rates were lower (30% vs. 40%–86%), prostate cancer detection rates/person biopsied were higher (49% vs. 31%–45%), and incidence of prostate cancer was 1.1% vs. 4.9% to 8.3%.ConclusionsAmong regular users of the VHA for healthcare, no disparities toward AA veterans exist in the use of prostate cancer screening and detection tools. Any differences in prostate cancer treatment outcomes are not likely because of inequalities in the use of prostate cancer screening or detection tools.