Cancer in pregnancy: disentangling treatment modalities.

Pregnancy-associated cancer constitutes an uncommon and difficult to manage clinical situation. It is defined as the cancer diagnosed from the first day of childbearing to 1 year post partum. Coexistence of cancer with pregnancy adds complexity to treatment recommendations, as both the mother and the fetus may be affected. The optimal therapeutic management of pregnant women with cancer diagnosis should take into account, apart from medical factors, a host of other parameters (ethical, psychological, religious, legal, etc). Unfortunately, this situation becomes more complex as more women delay childbearing, and consequently the incidence of cancer during pregnancy is constantly increasing. This manuscript summarises the general principles in managing pregnant patients with cancer and gives detailed instructions in the management of pregnant patients with breast cancer, ovarian cancer, melanoma, lymphoma, lung cancer, soft-tissue sarcoma and cervical cancer. Of note, management of pregnant women with cancer diagnosis should be performed in specialised centres with experience and all cases should be discussed in multidisciplinary meetings composed of multiple specialists (medical oncologists, obstetricians, surgeons, radiologists and paediatricians).

Adding the power of iodinated contrast media to the credibility of mammography in breast cancer diagnosis.

Dual-energy contrast-enhanced spectral mammography (CESM) represents a relatively new diagnostic tool adjunct to mammography. The aim of this study was to strengthen the breast imaging-reporting and data system (BIRADS) classification score in order to improve early breast cancer diagnosis. For this reason, we propose a sum score, termed malignancy potential score (MPS), incorporating the standard BIRADS score and our proposed CESM score. From September 2014 to September 2015, 216 females (age range, 26-85 years; mean age 54.6 years) underwent CESM evaluation of mammographic findings that were primarily assessed as BIRADS 2-5. 10 of these patients had bilateral findings; a total of 226 lesions were examined. High-energy image evaluation was based on the intensity of contrast enhancement of the lesion compared with background enhancement, categorized as Type -1, 0, 1 or 2 enhancement. Histopathology reports were compared with imaging assessment. 98 of 226 lesions were malignant and 128 of 226 lesions were benign. The area under the curve was 0.843, 0.888 and 0.917 for mammographic BIRADS score, CESM score and MPS, respectively, with p-value < 0.05. The sensitivity, specificity and accuracy rates were 91.83, 80.47 and 85.40%, respectively, when a best MPS cut-off point of 4 was used. The malignancy potential score (MPS) has higher diagnostic performance than digital mammography or CESM alone. MPS empowers the credibility of the digital mammography BIRADS score and our proposed type of enhancement in dual-energy CESM and is a diagnostic tool that increases the accuracy rate in early breast cancer diagnosis.

Breast Elastography: How We Do It.

In recent years, the use of elastography in addition to sonography has become a routine clinical tool for the characterization of breast masses. Studies have investigated the improvement of specificity in differentiating benign from malignant breast masses. Therefore, additional use of elastography could help reduce the number of unnecessary biopsies in benign breast lesions especially in category IV lesions of the ultrasound breast imaging reporting data system. Ultrasound elastography is a cheap, readily available, useful, quick, noninvasive method, but it needs specific training as well as acknowledging technical and pathological factors, which may influence it. Both strain and acoustic radiation force impulse (ARFI) methods have been evaluated in breast lesions. Whereas strain elastography results in qualitative imaging of tissue stiffness due to induced compression, ARFI elastography displays quantitative and qualitative information of tissue displacement. A standardized imaging protocol is essential for an adequate and effective examination, also helping reduce the dependence from operators. Furthermore, knowledge of pitfalls that can be encountered when ultrasound elastography is performed may help avoid erroneous image interpretation. In this article, we describe a practical examination protocol for both strain and ARFI elastography and demonstrate the elastographic imaging findings in benign and malignant breast lesions. Short video clips displaying the technique are included as supplementary material.

Expression of ARs in triple negative breast cancer tumors: a potential prognostic factor?

BACKGROUND/AIM: In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC). PATIENTS AND METHODS: Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score), clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression), and overall survival were evaluated. RESULTS: AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26-1.70, P=0.393). CONCLUSION: AR expression does not seem to play a prognostic role in TNBC.

Cumulative BRCA mutation analysis in the Greek population confirms that homogenous ethnic background facilitates genetic testing.

Screening for BRCA 1 and BRCA 2 mutations has long moved from the research lab to the clinic as a routine clinical genetic testing. BRCA molecular alteration pattern varies among ethnic groups which makes it already a less straightforward process to select the appropriate mutations for routine genetic testing on the basis of known clinical significance. The present report comprises an in depth literature review of the so far reported BRCA 1 and BRCA 2 molecular alterations in Greek families. Our analysis of Greek cumulative BRCA 1 and 2 molecular data, produced by several independent groups, confirmed that six recurrent deleterious mutations account for almost 60 % and 70 % of all BRCA 1 and 2 and BRCA 1 mutations, respectively. As a result, it makes more sense to perform BRCA mutation analysis in the clinic in two sequential steps, first conventional analysis for the six most prevalent pathogenic mutations and if none identified, a second step of New Generation Sequencing-based whole genome or whole exome sequencing would follow. Our suggested approach would enable more clinically meaningful, considerably easier and less expensive BRCA analysis in the Greek population which is considered homogenous.

Breast disorders in girls and adolescents. Is there a need for a specialized service?

INTRODUCTION: Minor breast concerns in childhood and adolescence are common and lead to increased anxiety among young patients and their families, particularly due to high correlation with breast cancer. However, most breast services aim at managing adults and triaging patients with breast cancer, whereas adolescent medicine specialists or pediatricians are usually not appropriately trained to identify and treat breast pathology. METHODS: We reviewed hospital records of all patients attending a pediatric and adolescent gynecology or breast clinic of a tertiary referral hospital, with a breast related symptom, between January 2009 and December 2011. We collected information regarding age at presentation, age at menarche, diagnosis, management and outcome. RESULTS: We identified 81 patients of which 11 presented with an abnormal nipple or areolar secretion, 33 had a palpable lump, 20 had mastitis, and 16 had unequal breast development. One patient presented with virginal breast hypertrophy. Three out of 11 of the patients with an abnormal secretion had a cyst identified on ultrasonography. Out of the palpable lumps 12 were fibroadenomas, 3 were phyllodes tumors, and 14 were cystic in nature. The phyllodes tumors and half of the fibroadenomas were removed. The remaining fibroadenomas remain under regular ultrasonographic follow-up. All cases of mastitis were treated conservatively and resolved with broad spectrum antibiotic treatment. CONCLUSION: In our series, no malignancies were identified. Although 8 patients required surgical treatment, the majority of cases were treated conservatively.

Discrepancies between ESMO and NCCN breast cancer guidelines: An appraisal.

An ever growing number of medical organizations, societies, working groups and governmental agencies issue algorithms i.e. guidelines, of decision making flowcharts in diagnosis and treatment in a variety of diseases. In the field of evidence-based diagnosis and treatment of breast cancer, a large number of guidelines are available both from medical associations and national health departments. Among the most appreciated and utilized comprehensive guides is the European Society for Medical Oncology (ESMO) Breast Cancer Guidelines and from the other side of the Atlantic the National Comprehensive Cancer Network (NCCN) Guidelines in Breast Cancer. Although there is much concordance between the guidelines from these two organizations, it is intriguing to locate their discrepancies also. The aim of this report is to present a number of different points between ESMO and NCCN in the whole spectrum of breast cancer management, from prevention and diagnosis to treatment and follow up. This systematic review was performed in accordance with the PRISMA guidelines using a predefined search strategy and summarizes in detail, the differences between ESMO and NCCN guidelines regarding genetic risk evaluation and screening, surgery, chemotherapy, endocrine treatment, targeted biological agents, radiotherapy, pregnancy and fertility and follow-up.

Low protein expression of MET in ER-positive and HER2-positive breast cancer.

AIM: The mesenchymal-epithelial transition factor (MET) is a receptor tyrosine kinase that plays a key role in cell survival, growth, angiogenesis and metastasis. Because its expression is frequently altered in tumors, MET is currently under investigation as a potential target for anticancer therapy. The purpose of the present study was to determine the prognostic value of tumor MET expression levels in patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-positive breast cancer, in order to strengthen the rationale for targeted therapy using MET inhibitors in this breast cancer subpopulation. MATERIALS AND METHODS: We determined the expression of MET in formalin-fixed paraffin-embedded surgical specimens of ER- and HER2-positive breast cancer by immunohistochemistry. RESULTS: Comparisons of MET expression with clinical parameters, including survival of the patients, were performed with MET expression as a dichotomized variable classified as high or low. Out of 78 tumors, 3 (3.8%) showed high MET expression. The analysis examining the association between MET and survival did not yield any statistically significant result regarding overall survival or disease-free survival. CONCLUSION: ER- and HER2-positive breast carcinomas do not exhibit high MET expression. This null finding, the first to be reported in the literature, is of great importance, since it indicates that this sub-group population is not proper candidate for clinical trials with MET inhibitors.

Breast cancer in women aged 25 years and younger.

OBJECTIVE: To evaluate breast cancer characteristics in women aged 25 years and younger. METHODS: This was a retrospective, nested, within-cases matched study. The study design was based on a two-phase protocol. In the first phase, stage, grade, histologic subtype, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status were compared between 28 patients (aged 25 years and younger) and 685 older premenopausal women (aged older than 25 years) with breast cancer. The second phase aimed to determine whether young patients exhibited worse prognosis when compared with older premenopausal women. RESULTS: Young patients presented at a more advanced stage (P=.012) and exhibited a higher grade (P=.018). No significant differences were noted regarding histologic subtype, estrogen receptor, and progesterone receptor status. Genetic testing for BRCA1 and BRCA2 mutations was performed in 12 of 28 young patients and mutations were found in 25% of them. Moreover, young women presented poorer overall survival (hazard ratio [HR] 4.30, 95% confidence interval [CI] 1.09-17.03) than their older counterparts, matched by histologic subtype, stage, and grade; a similar pattern was noted regarding relapse-free survival (HR 8.28, 95% CI 2.24-30.60). CONCLUSION: Breast cancer diagnosis in women aged 25 years and younger is uncommon; however, these patients present at a more advanced stage, with a higher grade, and exhibit poorer survival.

MMP-2 -1306C>T polymorphism in breast cancer: a case-control study in a South European population.

This case control study aims to investigate the role of MMP-2 -1306C>T polymorphism as a potential risk factor and possible prognostic marker for breast cancer in a South European population. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. MMP-2 -1306C>T polymorphism was genotyped; multivariate logistic regression as well as Cox regression analysis were performed. MMP-2 -1306C>T status was not associated with breast cancer risk either at the total sample or at the subanalyses on premenopausal and postmenopausal women. At the survival analysis, a trend towards a favorable association between MMP-2 -1306C>T allele and disease-free survival as well as overall survival was observed. Regarding subanalyses on ER-negative and ER-positive cases, the favorable association implicating MMP-2 -1306C>T allele was particularly evident among ER-positive cases; no significant associations emerged among ER-negative cases. MMP-2 -1306C>T polymorphism does not seem to be a risk factor for breast cancer in South European population; however, a trend towards a favorable association with survival has been observed.

Does pregnancy-associated breast cancer imply a worse prognosis? A matched case-case study.

BACKGROUND: Significant controversy exists in the literature regarding the role of pregnancy in the prognosis of breast cancer. We designed a matched case-case study, matching pregnancy-associated breast cancer (PABC) cases with breast cancer cases for stage, age, and year of diagnosis. PATIENTS AND METHODS: 39 consecutive cases of PABC were matched with 39 premenopausal cases of breast cancer. Univariate and multivariate survival analyses followed by adjustment for stage, grade, estrogen receptor status, and age at diagnosis, were performed. RESULTS: Regarding overall survival (OS), univariate analysis pointed to longer OS in non-PABC cases vs. PABC cases. Accordingly, a more advanced stage predicted shorter survival. In the multivariate analysis, the independent aggravating effect mediated by pregnancy persisted. Interestingly, a post hoc nested analysis within PABC cases indicated that the 3rd trimester pointed to shorter OS. The aforementioned results on OS were also replicated during the examination of relapse-free survival. CONCLUSION: Implementing a matched case-case design, the present study points to pregnancy as a poor prognostic factor for breast cancer.

Taxanes for breast cancer during pregnancy: a systematic review.

Landmark studies have established taxanes in the treatment of patients with breast cancer; however, recommendations regarding their administration during pregnancy are controversial. The present systematic review aims to synthesize all available data that stem exclusively from breast cancer case series to evaluate the efficacy and safety of taxanes during pregnancy. Overall, 16 studies (50 pregnancies) were eligible for the systematic review according to prisma guidelines. The mean age of patients with breast cancer at pregnancy was 34.6 years. The gestational age (GA) at chemotherapy administration varied from 12 to 36 weeks. The mean GA at delivery was 35.9 weeks. The mean weight of babies at delivery was 2380 g. In 76.7% of cases, a completely healthy neonate was born; in the remaining cases, a neonate who was dystrophic and premature, one with mild hydrocephalus, one with signs of bacterial sepsis, one with hyperbilirubinemia, one with apnea of prematurity, respiratory distress syndrome and gastroesophageal reflux, one with meconium-stained fluid, and another neonate with neutropenia and pyloric stenosis were reported. Ninety percent of children were completely healthy, with a median follow-up of 16 months; in the remaining cases, one child with recurrent otitis media, one with immunoglobulin A deficiency and mild constipation, and another child with delayed speech were reported. In conclusion, available data suggest that taxanes may potentially play a promising role in the optimal therapeutic strategy of patients with breast cancer diagnosed during pregnancy.

HTERT MNS16A polymorphism in breast cancer: a case-control study.

This case-control study aims to investigate the role of HTERT MNS16A polymorphism as a potential risk factors and/or a prognostic marker for breast cancer. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. HTERT MNS16A polymorphism was genotyped (L: long allele, S: short allele); multivariate logistic regression was performed. No significant association was noted either at the overall analysis (OR = 1.57, 95 % CI 0.84-2.93 for heterozygous LS carriers; OR = 1.02, 95 % CI 0.54-1.95 for homozygous SS carriers) or at the subanalyses in premenopausal and postmenopausal women. With respect to survival analysis, HTERT MNS16A polymorphism was not associated with either disease-free survival or overall survival. HTERT MNS16A polymorphism does not seem to be a risk factor for breast cancer in the Caucasian Greek population. Further, larger studies from other countries and subjects seem to be needed as this novel polymorphism is being examined in depth.

HSP90, HSPA8, HIF-1 alpha and HSP70-2 polymorphisms in breast cancer: a case-control study.

This case control study aims to investigate the role of HSP90 Gln488His (C > G), HSP70-2 P1/P2, HIF-1 alpha C1772T and HSPA8 intronic 1541-1542delGT polymorphisms as potential risk factors and/or prognostic markers for breast cancer. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy cases were recruited. The above mentioned polymorphisms were genotyped; multivariate logistic regression was performed. HSP90 GG (His/His) genotype was associated with elevated breast cancer risk. Similarly, the allele dose-response model pointed to increase in breast cancer risk per G allele. HSP70-2 P1/P2, HSPA8 intronic 1541-1542delGT and HIF-1 alpha polymorphisms were not associated with breast cancer risk, as evidenced by the dose-response allele models. The positive association between HSP90 G allele and breast cancer risk seemed to pertain to both premenopausal and postmenopausal women. With respect to survival analysis, none of the aforementioned polymorphisms was associated with either disease-free survival or overall survival. HSP90α Gln488His polymorphism seems to be a risk factor for breast cancer. On the other hand, our study did not point to excess risk conferred by HSPA8 1541-1542delGT, Hsp70-2 P1/P2 and HIF-1α C1772T.

Low salivary testosterone levels in patients with breast cancer.

BACKGROUND: Correlation between circulating sex steroid levels and breast cancer has been controversial, with measurement of free, or bioavailable hormone rarely available. Salivary hormone levels represent the bioavailable fraction. To further elucidate the role of endogenous hormones in breast cancer, we aimed to assess correlation between salivary sex steroid levels and breast cancer prevalence. METHODS: Salivary hormone levels of testosterone (T), Estradiol (E2), Progesterone (P), Estriol (E3), Estrone (E1), DHEAS and Cortisol (C) were measured by Enzyme Immunoassay (EIA) in 357 women with histologically verified breast cancer and 184 age-matched control women. RESULTS: Salivary T and DHEAS levels were significantly lower in breast cancer cases vs. controls (27.2+13.9 vs. 32.2+17.5 pg/ml, p < 0.001 for T and 5.3+4.3 vs. 6.4+4.5 ng/ml, p = 0.007 for DHEAS). E2 and E1 levels were elevated and E3 levels were lowered in cases vs. controls. CONCLUSIONS: Salivary T levels, representing the bioavailable hormone, are significantly lower in women with breast cancer compared to age-matched control women. These findings support the protective role of bioavailable testosterone in counteracting the proliferative effects of estrogens on mammary tissue.

What have we really learned from 'LIBERATE' trial?

LIBERATE trial reports that Tibolone use increases the risk of recurrence in breast cancer patients with vasomotor symptoms. However, there are some uncertainties and weak points in the study. Emerged questions are if interpretation of the results could be extrapolated to all breast cancer patients or there are specific subgroups that could use Tibolone without increasing relapse rate.

Reinforced iliotibial tenodesis for chronic anterolateral instability of the knee: a 6-year follow-up.

Reinforced iliotibial tenodesis is an extra-articular procedure to eliminate anterolateral instability of an anterior cruciate ligament-deficient knee. The procedure carries a low complication rate and offers an easy rehabilitation program. This study evaluated the use of reinforced iliotibial tenodesis in a select group of 52 patients with a mean age of 41 years (range: 38-50 years). Obese patients, professional athletes, and patients with more complex injuries (eg, concomitant posterior cruciate or medial collateral ligament injuries) were excluded. Results are encouraging after a mean follow-up of 6 years (range: 2-10 years). Although 24 patients had a positive anterior drawer or Lachman test, none had a positive pivot test. In addition, all patients reported giving way was eliminated after surgery.