Nilufer Bulut

Sonographic and Electrodiagnostic Evaluations in Patients With Aromatase Inhibitor-Related Arthralgia

PURPOSE To investigate the prevalence of arthralgia in breast cancer patients taking aromatase inhibitors (AIs) and perform a detailed rheumatologic assessment including autoimmune serology, musculoskeletal sonography, and electromyography (EMG) in these patients. PATIENTS AND METHODS Postmenopausal patients with stage I to III breast cancer who were taking adjuvant AIs were enrolled (n = 92). Patients who were not receiving hormone treatment were included as a control group (n = 28). Musculoskeletal sonography and EMG were applied to the patients and the controls along with markers of autoimmunity. RESULTS Thirty patients (32.6%) reported to have AI-related new-onset or worsening arthralgia. The most commonly affected joints were knee (70%), wrist (70%), and small joints of the hand (63%). Patients taking AIs had increased tendon thicknesses compared with those who never received AIs (P < .001). Patients with AI-related arthralgia had higher rates of effusion in hand joints/tendons than those without arthralgia (P = .033). More patients with AI-related arthralgia had EMG findings consistent with carpal tunnel syndrome (CTS) than those without arthralgia (P = .024). No significant difference was observed in erythrocyte sedimentation rates, C-reactive protein, antinuclear antibody, antidouble stranded DNA antibody, rheumatoid factor, or anticyclic citrullinated peptide levels between patients and controls or between those with and without arthralgia. CONCLUSION Patients with AI-related arthralgia often show tenosynovial changes suggesting tenosynovitis, exerting local problems but lacking a systemic inflammatory component. Our finding of increased CTS frequency also supports this hypothesis.

Dasatinib may also inhibit c-Kit in triple negative breast cancer cell lines

In their interesting paper, Finn et al. [1] reported that dasatinib selectively inhibits growth of basal-type/’’triplenegative’’ breast cancer cell lines growing in vitro. Authors discussed that this activity may be happened through the inhibition of src and/or bcl kinase. Interestingly, by using a panel of 21 basal-like tumors, Nielsen et al. [2] showed that triple-negative breast cancer cell was typically immunohistochemically negative for estrogen receptor and HER2 but positive for basal cytokeratins, HER1, and/or c-KIT. In another study it was shown that dasatinib also inhibits c-Kit in addition to inhibition of src and bcl kinases [3]. Therefore, inhibitory activity of dasatinib on the growth of triple-negative breast cancer cell lines may also be attributed to inhibition of c-Kit in these cell lines.

Response to taxanes in triple negative breast cancer

To The Editor, We read with great interest the article by Torrisi et al. [2]. In their preoperative treatment of locally advanced triple negative breast cancer, cisplatin containing chemotherapy followed by paclitaxel induced a high pCR rate. Authors in the discussion part state that their results support lower responsiveness to taxanes if compared with cisplatin in BRCA1 defective breast cancer. Hayes et al. [1] study evealuated HER2 and response to paclitaxel in node-positive breast cancer. In this retrospective analysis of CALGB 9344/INT0148 study in which randomly selected 1,500 women from 3,121 women with node-positive breast cancer had been been randomly assigned to receive adjuvant doxorubicin plus cyclophosphamide (for four cycles), followed by four cycles of paclitaxel or observation. In the subgroup analysis according to estrogen receptor and HER-2 receptor status, patients with a HER2-negative and estrogen-receptor negative breast cancer beneWted from paclitaxel sigiWcantly (P = 0.002). This information may indicate that in long-term run, triple negative breast cancer patients may get beneWt from addititon of paclitaxel to standard regimen.

Vitamin D intake may be a predictor of response to aromatase inhibitors in postmenopausal women with hormone receptor positive breast cancer

To the Editor, The importance of estrogen in the development and progression of breast cancer has been recognized for some time. Main estrogen biosynthesis in postmenopausal women is catalyzed by P450 aromatase, encoded by the CYP19 gene. Aromatase inhibitors (AI) were designed to inhibit estrogen synthesis in the postmenopausal women. Based on the results of large trials with AI in advanced, adjuvant, and neoadjuvant settings, third generation AI are widely accepted as a part of treatment for postmenopausal women with hormone-receptor positive breast cancer [1]. There are no standard biologic predictors of response to AI. Vitamin D intake is a part of treatment of postmenopausal osteoporosis. In addition, AI itself leads to osteoporosis by decreasing circulating estrogen levels in postmenopausal women necessitating osteoporosis treatment including vitamin D. Interestingly, it has been demonstrated that the vitamin D is a potent stimulator of CYP19 (P450 aromatase gene) transcription [2]. Therefore, concomitant use of vitamin D and AI may lead to resistance to AI in postmenopausal women with hormone-receptor positive breast cancer. Further prospective studies are needed to confirm this proposal.

Multimodality treatment in the management of anorectal melanoma: a case report and review of the literature.

Anorectal melanoma represents approximately 0.2-1% of all malignant melanomas and has a poor prognosis, with a median survival of 8 to 23 months after the time of diagnosis. The typical treatment modalities include surgery, radiotherapy and chemotherapy. The particular approach taken depends on the patients status and disease stage. Although there are different treatment options for this rare condition, there are not enough studies on multimodality treatment. Here, we present the case of a 54-year-old female with anorectal melanoma that had metastasized to an inguinal lymph node. She underwent local excision of the rectal mass and inguinal lymph-node dissection. Temozolomide treatment was started after radiotherapy and was given for 24 months. Follow-up revealed that the patient has been doing well with no signs of recurrence three years after the completion of treatment. We aim to discuss combined treatment modalities for ARM in light of the pertinent literature.

Pathological characteristics of very young (≤30 years) breast cancer patients: a single-institution experience from Turkey

Breast cancer rarely occurs in young women. Our knowledge about disease presentation, prognosis and treatment effects is largely dependent upon older series. Breast cancer in women <35 years of age occurs rarely (2%–4% of all breast cancer). Age <35 is an independent risk factor of recurrence and death [1]. There is little information about very young breast cancer patients (£30 years of age) in the literature. The aim of the study was to compare pathological risk factors of women with breast cancer aged £30 (very young group) with women with breast cancer aged 31–50 years (young group). One thousand and thirty-eight consecutive breast cancer patients presenting at Hacettepe University Institute of Oncology between years 2004 and 2007 were evaluated. In all, 422 (40.0%) of the patients were premenopausal and £50 years; 116 (11.1%) and 44 (4.2%) patients were £35 and £30 years of age, respectively. Median ages of the diagnosis in very young and young breast cancer groups were 28 and 41, respectively. In the ‘very young’ group, when compared with the ‘young’ breast cancer patients, percentages of tumors classified as estrogen receptor negative (48.5% versus 38.1%, P = 0.26), progesterone receptor negative (43.3% versus 39.4%, P = 0.70), HER2/neu positive (38.1% versus 22.2%, P = 0.23), and grade 3 (52.9% versus 39.4%, P = 0.14) tend to be higher although statistically not significant. Triple-negative breast cancers were more frequent in very young groups (30.4% versus 18.6%, P = 0.21). There were no statistical differences in extracapsular extension in metastatic axillary nodes, neural invasion, and lymphovascular invasion of tumors between the two age groups. There were also no differences between the two groups for pathological tumor size (T), frequency of positive lymph nodes (N), and distant metastasis at diagnosis (M). In our small cohort study population, we observed that very young patients (£30) tended to have poorer pathological prognostic factors compared with the young breast cancer patients. In our study population, the percentage of younger breast cancer (£35) (11.1%) is higher compared with the literature [2–5]. Tumors occurring in very young patients are reported to have a particularly aggressive biological behavior leading to a somewhat unfavorable prognosis, which was described extensively in the preadjuvant systemic therapy era [3, 6]. Several reports about age and prognosis as seen in our report conclude that features like higher grade represent a relevant aspect for discriminating between very young and young premenopausal breast cancer patients [1–6]. The results of the present study indicate that very young patients in our institution are having more high grade, triple-negative and HER-2-positive tumors representing poorer prognostic features than young premenopausal breast cancer patients.

OSTEONECROSIS OF THE JAW

398 JADA, Vol. 139 http://jada.ada.org April 2008 available data and develop and promote guidelines for oral health care providers in the best interests of our patients. Our survey and Dr. Huber’s letter point to the need for continuing research and development of guidelines in detection, diagnosis, intervention and follow-up of oral premalignant lesions that falls within the scope of dentistry. Joel Epstein Professor and Head Department of Oral Medicine and Diagnostic Sciences College of Dentistry and Director, Interdisciplinary Program in Oral Cancer Prevention, Detection and Treatment Chicago Cancer Center University of Illinois at Chicago

Role of trastuzumab in patients with brain metastases from Her2 positive breast cancer.

To the Editor, We read with great interest the article by Bartsch et al. [1] in which they indicated that trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer. The authors presented some supportive data for the trastuzumab use in these patients. We want to add one more. Blood-brain-barrier (BBB) disruption can also be induced by radiation therapy. Radiotherapy with doses of 20–30 Gy with fraction size of 2 Gy may be used to increase the permeability of the BBB [2]. A Her2 level-dependent sensitization to radiation-induced apoptosis by trastuzumab in a panel of breast cancer cell lines has been observed [3]. Radiosensitization by trastuzumab was further demonstrated by a reduced clonogenic survival of breast cancer cells after radiation. Having given information above, we further suggest that trastuzumab should not be discarded in combination with radiotherapy as a treatment option in patients previously treated or during trastuzumabbased therapy for metastatic breast cancer.

Does breast cancer associated with CHEK2 1100delC carry characteristics of basal phenotype

In their interesting paper, Chekmariova et al. [1] found potentially high clinical relevance of CHEK2 1100delC in breast cancer patients of Russian origin. However, they did not mention clinical-pathological characteristics of these breast cancer patients with CHEK2 1100delC. Similar to BRCA1, CHEK2 is a tumor suppressor and acts in response to DNA double strand damage [2]. Furthermore germ-line BRCA1 mutations result in breast cancers that are highly likely carrying characteristics of basal phenotype. Basal-like breast carcinomas are a distinct clinical and pathological, characterized by high histological grade, lack of hormone receptors and HER2 expression [3]. Recent study showed that CHEK2 1100delC heterozygosity is associated with a 3-fold risk of breast cancer in women in the general population [4]. When we review tumor characteristics of these 13 breast cancer patients associated with CHEK2 1100delC heterozygosity in this study, these patients are mostly high-intermediate grade (77%) and estrogen receptor negative (77%). However, HER-2 status and progesterone receptor were not reported in this study. In conclusion, breast cancer patients associated with CHEK2 1100delC heterozygosity may represent characteristics of basal-phenotype, molecular gene signature analysis and clinical-pathological characteristics of breast cancer patients with CHEK2 1100delC may give us some clue to better understand this specific group of breast cancer patients.