Correction of Poland's Syndrome: Case Report and Review of the Current Literature.

BACKGROUND: Poland's syndrome, a rare congenital anomaly, consists of unilateral absence of the pectoralis major muscle, ipsilateral brachysyndactyly, and occasionally associated other malformations of the anterior chest wall, mamilla, and mamma. CASE REPORT: In the case of a 32-year-old woman, marked hypoplasia of the right breast and the right nipple, malformation of the right upper limb with brachysyndactyly and microdactyly were noted, all present since birth. This paper describes the surgical technique and possible complications of reconstruction of the chest wall deformity with a solid silicone implant and a latissimus dorsi flap. The current literature on the topic is reviewed. CONCLUSION: The surgical method with autologous material and implants is a sufficient technique for chest wall reconstruction and gives a good long-term result in case of Poland's syndrome.

Polymorphisms of the endothelial nitric oxide synthase gene in breast cancer.

Nitric oxide (NO) is known to be critically involved in breast carcinogenesis. Genetic polymorphisms of the gene encoding for endothelial nitric oxide synthase (Nos3), the enzyme catalyzing the production of the NO, are known to predispose to malignant disease. Whether these polymorphisms also influence breast cancer risk is unknown. In the present case-control study, we ascertained 2 polymorphisms of the Nos3 gene cluster (Nos3 exon 7 Glu298Asp and a 27-base pair repeat in intron 4 of Nos3) in 269 Caucasian patients with breast cancer and 244 healthy controls using pyrosequencing and PCR, respectively. Presence of the exon 7 Nos3 polymorphism predisposed women to breast cancer (p=0.03, Odds ratio [95% Confidence Intervals]=1.9 [1.1-3.6]), but was not associated with any clinico-pathological parameters. No significant associations were ascertained with respect to the intron 4 Nos3 polymorphism. In our series, presence of the mutant exon7 Nos3 polymorphism was associated with an increased risk for breast cancer in Caucasian women.

Interleukin-1 and interleukin-6 gene polymorphisms and the risk of breast cancer in caucasian women.

PURPOSE: Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. Interleukin (IL)-1 and IL-6 are crucially involved in breast carcinogenesis. Whether polymorphisms of the genes encoding IL-1 (IL1) and IL-6 (IL6) also influence breast cancer risk is unknown. EXPERIMENTAL DESIGN: In the present case-control study, we ascertained three polymorphisms of the IL1 gene cluster [-889 C/T polymorphism of the IL1alpha gene (IL1A), -511 C/T polymorphism of the IL1beta promoter (IL1B promoter), a polymorphism of IL1beta exon 5 (IL1B exon 5)], an 86-bp repeat in intron 2 of the IL1 receptor antagonist gene (IL1RN), and the -174 G/C polymorphism of the IL6 gene (IL6) in 269 patients with breast cancer and 227 healthy controls using PCR and pyrosequencing. RESULTS: Polymorphisms within the IL1 gene cluster and the respective haplotypes were not associated with the presence and the phenotype of breast cancer. The IL6 polymorphism was significantly associated with breast cancer. Odds ratios for women with one or two high-risk alleles versus women homozygous for the low-risk allele were 1.5 (95% confidence interval, 1.04-2.3; P = 0.04) and 2.0 (95% confidence interval, 1.1-3.6; P = 0.02), respectively. No association was ascertained between presence of the IL6 polymorphism and various clinicopathologic variables. CONCLUSIONS: Although polymorphisms within the IL1 gene cluster do not seem to influence breast cancer risk or phenotype, presence of the -174C IL6 allele increases the risk of breast cancer in Caucasian women in a dose-dependent fashion.

Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group.

PURPOSE: Dose-dense and sequential administration of cytotoxic drugs are current approaches to improve outcomes in patients with early-stage breast cancer. METHODS: This phase III study investigated 913 women with untreated operable breast cancer (T2-3, N0-2, M0) randomly assigned to receive either doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 every 14 days for four cycles with filgrastim support (ADOC), or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 21 days followed by docetaxel 100 mg/m2 every 21 days for four cycles each (AC-DOC). The primary end point was the incidence of pathologic complete (invasive and noninvasive) response (pCR) in the breast and axillary nodes. Secondary end points were predictors for pCR, clinical response, rate of breast conservation, and safety. RESULTS: A pCR was achieved in 94 patients (10.6%), but the likelihood was significantly greater with AC-DOC (14.3%; n = 63) than with ADOC (7.0%; n = 31) (odds ratio, 2.22; 90% CI, 1.52 to 3.24; P < .001). Independent predictors of attaining a pCR included the use of sequential therapy, high tumor grade, and negative hormone receptor status. The response rates detected by palpation and by imaging were significantly higher with AC-DOC (85.0% and 78.6%, respectively) than with ADOC (75.2% and 68.6%, respectively; both P values < .001). The rate of breast-conserving surgery was 63.4% for AC-DOC and 58.1% for ADOC (P = .05). Predominant grade 3/4 toxicities were leucopenia (AC-DOC, 74.2%; ADOC, 53.7%) and neutropenia (AC-DOC, 66.4%; ADOC, 44.7%) but were infrequently associated with fever (AC-DOC, 4.6%; ADOC, 3.1%). CONCLUSION: Sequential AC-DOC is more effective at inducing pCR than dose-dense ADOC as preoperative treatment for patients with operable breast cancer.

MR imaging of the contralateral breast in patients after breast-conserving therapy.

A study was undertaken to assess the diagnostic accuracy of contrast-enhanced MR mammography (MRM) of the contralateral breast in patients treated by breast-conserving therapy previously. A total of 119 patients underwent 145 standardized dynamic MR studies (1 T, T1-weighted 3D FLASH, 0.2 mmol Gd-DTPA/kg body weight). We retrospectively evaluated the results of conventional methods and MRM. A total of 11 contralateral carcinomas were present (detection rate 9%). The interval between treatment of the first primary and identification of contralateral malignancy was 9-80 months (mean 33 months). The MRM allowed detection of four otherwise occult malignancies. One of 11 cancer was missed on MRM due to benign appearance of enhancement. Compared with conventional methods MRM improved sensitivity (91 vs 64%) and specificity (90 vs 84%), respectively. This study suggests that additional MRM of the contralateral breast increases the diagnostic accuracy not only by enhancing the detection of second cancers but also by reducing false-positive results.

Dose-dense biweekly doxorubicin/docetaxel versus sequential neoadjuvant chemotherapy with doxorubicin/cyclophosphamide/docetaxel in operable breast cancer: second interim analysis.

Timing of systemic treatment in primary operable breast cancer is subject to extensive investigation, suggesting that pathologic complete remission (pCR) might improve survival in this setting. The German Adjuvant Breast Cancer Group previously demonstrated the feasibility of a dose-dense biweekly schedule of 4 cycles doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 (ddAT) +/- tamoxifen in the neoadjuvant setting to yield a pCR of 9.7% (Gepardo trial). Patients assigned to ddAT received prophylactic granulocyte colony-stimulating factor support (5 micro g/kg days 5-10). The current study (GeparDUO) was designed to assess whether the pCR rate, including no viable invasive and preinvasive tumor cells, achieved with ddAT was equivalent to sequential administration of doxorubicin/cyclophosphamide followed by docetaxel (AC-DOC) over 24 weeks in primary operable breast cancer. From June 1999 to September 2001, 913 patients were enrolled in this trial. In total, 395 patients randomized before August 1, 2000, were included in the second interim analysis. Safety data were available from 369 patients (ddAT, n = 191; AC-DOC, n = 178) demonstrating that toxicity of both regimens was tolerable. Grade 3/4 neutropenia occurred in 39.8% of patients receiving ddAT and in 69.3% of patients treated with AC-DOC. Efficacy data were available in 378 patients. A pCR occurred in 14.8% of the primary breast tumors. According to the recommendations of the data monitoring committee, recruitment to the study was halted as of September 2001 (n = 913/1000) due to the significant difference in pCR rates observed between the treatment arms. Surgery was documented in 380 patients. Breast conservation was possible in 288 cases (75.8%). The application of both schedules is safe and feasible in an outpatient setting. Although, results obtained from this interim analysis are encouraging, caution is recommended until the results obtained show statistical difference in pCR.

Histological category and expression of hormone receptors in ductal carcinoma in situ of the breast.

BACKGROUND: While the role of estrogen receptor (ER) and progesterone receptor (PR) status in invasive breast cancer has been clinically established, data with respect to their role in ductal carcinoma in situ of the breast (DCIS) are sparse. PATIENTS AND METHODS: We reviewed 120 consecutive patients with DCIS I-III. Detailed histological categorization and immunohistochemical staining for ER and PR were performed and correlated with clinical data. RESULTS: DCIS I, DCIS II, and DCIS III were found in 51, 36 and 33 patients, respectively. Comedo-type tumors (p<0.001), presence of tumor necrosis (p<0.001) and absence of ER (p=0.005) were significantly associated with poorly-differentiated DCIS. No association was ascertained between PR expression and grade of DCIS. Hormone receptor expression was independent of the patients' menopausal status. CONCLUSION: We support the assumption that DCIS I-III is morphologically and biologically heterogeneous. Our results contribute further data on the role of ER and PR in the pathogenesis and progression of DCIS.

The correlation between immunohistochemically-detected markers of angiogenesis and serum vascular endothelial growth factor in patients with breast cancer.

BACKGROUND: As angiogenesis is known to be a crucial factor in breast cancer growth, numerous studies have examined angiogenic markers in breast cancer. Their definite role, however, has not been fully elucidated. MATERIALS AND METHODS: We investigated intratumoral microvessel density (MVD), Vascular Endothelial Growth Factor (VEGF) and its receptor flk-1, and serum VEGF in 46 patients with breast cancer prior to surgery. RESULTS: Median serum VEGF in patients with breast cancer was 257.5 pg/mL (range, 21.9 to 899.6). Serum VEGF showed a significant correlation with tumor stage, but not with lymph node involvement, histological grade, estrogen and progesterone receptor status. Increased MVD was associated with advanced tumor stage (p=0.05) and high tumor grade (p<0.001). A linear significant correlation between elevated serum VEGF and increased MVD was ascertained (p=0.02). CONCLUSION: Our results suggested that angiogenesis as reflected by immunohistochemically-detected MVD and serum VEGF, is involved in breast cancer growth and lymphatic spread.

Suppression of unspecific enhancement on breast magnetic resonance imaging (MRI) by antiestrogen medication.

AIMS AND BACKGROUND: The value of breast MRI may be impaired by unspecific enhancement. This may leave patients with difficult-to-assess breast tissue with an uncertain diagnosis. We examined whether this unspecific enhancement (which is mostly due to proliferative or hyperplastic changes of benign breast tissue) may be suppressed by antiestrogen medication. METHODS: In a trial of treatment, 10 peri- or postmenopausal patients who exhibited diffuse and/or focal enhancement on breast MRI before tamoxifen medication agreed to undergo a short-term tamoxifen treatment. MRI monitoring was performed 2, 4 and 8 weeks after onset of antiestrogen therapy (tamoxifen, 30 mg per day). RESULTS: Six patients showed a significant decrease of enhancement. Unchanged (n = 3) or increased (n = 1) enhancement was seen in 4 patients. One of the three patients with unchanged enhancement proved to have diffuse lobular carcinoma in situ. CONCLUSIONS: Part of the unspecific enhancement seen on breast MRI can probably be suppressed by short-term antiestrogen medication.

Polymorphisms of the endothelial nitric oxide synthase gene in ovarian cancer.

OBJECTIVE: The free radical nitric oxide is known to be critically involved in ovarian carcinogenesis by inducing apoptosis and by mediating various cytostatic and cytotoxic effects, but also by promoting growth, invasion, and metastasis. METHODS: We investigated two polymorphisms (exon 7 Glu298Asp and a 27-bp repeat in intron 4) of the gene encoding endothelial nitric oxide synthase (Nos3) in 130 patients with ovarian cancer, 26 patients with borderline ovarian cancer, and 133 healthy age-matched Caucasian women using PCR and pyrosequencing, respectively. RESULTS: Genotypes and allelic frequencies did not differ between patients with ovarian cancer and controls. Within the ovarian cancer group, however, the presence of at least one mutant allele of intron 4 was associated with advanced tumor stage and positive lymph node involvement, but not with tumor grading. The presence of the mutant allele of exon 7 was not associated with the investigated clinicopathological parameters. No correlation with patients' overall and disease-free survival was ascertained. CONCLUSIONS: We are the first to report on Nos3 polymorphisms in ovarian cancer. Allelic variation within intron 4 of Nos3 is associated with an advanced tumor stage and positive lymph node involvement in ovarian cancer.

Preservation of histopathologic assessment by use of a special technique for tissue inactivation by radiofrequency.

Thermoinactivation is under investigation as a new method of cancer treatment. Prior histopathologic verification has been indispensable. Our experiments show that thermoinactivation is in principle possible without destroying histopathologic morphology, if the temperature stays within certain limits. It could thus become applicable already before diagnostic biopsy, which might be used to avoid any potential spread during biopsy and before definitive surgery.