Beth Ann Ditkoff

Volatile Markers of Breast Cancer in the Breath

Abstract: Breast cancer is accompanied by increased oxidative stress and induction of polymorphic cytochrome P‐450 mixed oxidase enzymes (CYP). Both processes affect the abundance of volatile organic compounds (VOCs) in the breath because oxidative stress causes lipid peroxidation of polyunsaturated fatty acids in membranes, producing alkanes and methylalkanes which are catabolized by CYP. We performed a pilot study of breath VOCs, a potential new marker of disease in women with breast cancer. This was a combined case‐control and cross‐sectional study of women with abnormal mammograms scheduled for a breast biopsy. Breath samples were analyzed by gas chromatography and mass spectroscopy in order to determine the breath methylated alkane contour (BMAC), a three‐dimensional display of the alveolar gradients (abundance in breath minus abundance in room air) of C4–C20 alkanes and monomethylated alkanes. BMACs in women with and without breast cancer were compared using forward stepwise discriminant analysis. Two hundred one breath samples were obtained from women with abnormal mammograms and biopsies read by two pathologists. There were 51 cases of breast cancer in 198 concordant biopsies. The breath test distinguished between women with breast cancer and healthy volunteers with a sensitivity of 94.1% (48/51) and a specificity of 73.8% (31/42) (cross‐validated sensitivity 88.2% (45/51), specificity 73.8% (31/42)). Compared to women with abnormal mammograms and no cancer on biopsy, the breath test identified breast cancer with a sensitivity of 62.7% (32/51) and a specificity of 84.0% (42/50) (cross‐validated sensitivity of 60.8% (31/51), specificity of 82.0% (41/50)). The negative predictive value (NPV) of a screening breath test for breast cancer was superior to a screening mammogram (99.93% versus 99.89%); the positive predictive value (PPV) of a screening mammogram was superior to a screening breath test (4.63% versus 1.29%). A breath test for markers of oxidative stress accurately identified women with breast cancer, with an NPV superior to a screening mammogram. This breath test could potentially be employed as a primary screen for breast cancer. Confirmatory studies in larger groups are required.

Internet use and social support in women with breast cancer.

Many Web sites offer information to breast cancer patients, who are increasingly using these sites. The authors investigated the potential psychological benefits of Internet use for medical information by breast cancer patients. Of the 251 women approached, 188 were successfully interviewed (74.9%). Forty-two percent used the Internet for medical information related to breast health issues and did so for an average of 0.80 hr per week. The Interpersonal Support Evaluation List and the UCLA Loneliness Scale, with results controlled for covariates, showed that Internet use for breast health issues was associated with greater social support and less loneliness than Internet use for other purposes or nonuse. Breast cancer patients may obtain these psychological benefits with only a minimal weekly time commitment.

Detection of circulating thyroid cells in peripheral blood

BACKGROUND Detection of circulating malignant thyroid cells may provide a method to identify postoperative patients at risk for metastatic thyroid cancer. METHODS On the basis of tissue specificity of thyroglobulin gene expression and the sensitivity of the reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, we performed RT-PCR using primers for thyroglobulin on blood samples from patients with thyroid disease to detect thyroglobulin RNA transcripts. Postoperative peripheral blood samples from 100 patients, including patients with known metastatic thyroid cancer (six papillary and three follicular), thyroid cancer and no evidence of current metastases (63 papillary, 10 follicular, and five patients with both papillary and follicular), benign thyroid disease (six nontoxic nodular goiters), and normal volunteers (seven). RESULTS Thyroglobulin transcripts were detected in nine of nine patients with metastatic thyroid cancer, seven of 78 patients with thyroid cancer and no current metastases (although of these seven patients, five had a history of metastatic disease that had been previously treated by surgery, one had a coexisting parathyroid cancer, and one had both papillary and follicular thyroid cancers), zero of six patients with benign thyroid disease, and zero of seven normal volunteers. Identity of amplicons was confirmed by restriction enzyme digestion and by cloning and sequencing of RT-PCR amplified thyroglobulin fragment (the latter in a limited number of cases). CONCLUSIONS These data indicate that RT-PCR can be used to detect thyroglobulin mRNA in peripheral blood. The presence of these transcripts correlates with the existence of extrathyroidal disease.

The Management of Lobular Neoplasia Identified on Percutaneous Core Breast Biopsy

Abstract: The management of lobular neoplasia (LN) found on percutaneous core biopsy remains a clinical dilemma. The purpose of this study was to establish guidelines for the management of LN when obtained on percutaneous core needle biopsy. A retrospective review of the Breast Imaging Tissue Sampling Database at New York Presbyterian Hospital–Columbia Comprehensive Breast Center was performed from 1998 to 2000. A total of 1460 percutaneous core breast biopsies were performed using 11‐ or 14‐gauge needles with LN identified in 43 biopsies from 34 patients. Eleven biopsies were ultrasound guided for nonpalpable masses and 32 were stereotactically guided for mammographically detected densities (10) and microcalcifications (22). The 43 LN biopsies were divided into three groups based on additional findings associated with LN on core biopsy: group I (n = 19), LN with invasive cancer or ductal carcinoma in situ (DCIS); group II (n = 11), LN plus a second indication for open surgical biopsy, such as atypical ductal hyperplasia (ADH), radial scar, phyllodes tumor, or intraductal papilloma; and group III (n = 13), LN plus benign fibrocystic changes. In group I, 19 of 19 biopsies (100%) yielded invasive cancer or DCIS on surgical biopsy versus 3 of 11 (27%) for group II, and 1 of 13 (8%) for group III. Outcomes in group III are described as follows: three patients were lost to follow‐up, three patients did not undergo surgical biopsy but demonstrated more than 1 year of mammographic stability following core biopsy. Of the remaining seven patients, two had LN and ADH on surgical biopsy (one had a contralateral cancer), one had atypical lobular hyperplasia (with a contralateral cancer), two had LN and benign fibrocystic changes, one had LN and intraductal papilloma, and one had LN and invasive ductal carcinoma (IDC) with DCIS (with a contralateral cancer). These results suggest that surgical biopsy is indicated for patients with LN when found on core biopsy and when the biopsy demonstrates invasive cancer, DCIS, or other indications for surgical biopsy such as ADH, or in the examination of a patient with a synchronous contralateral breast cancer. The diagnosis of LN alone without these indications on percutaneous biopsy may not warrant routine surgical biopsy. 

Acquired arteriovenous fistula of the breast.

P ercutaneous biopsies have become a valuable tool for the evaluation of masses in the breast. For nonpalpable masses, ultrasound core biopsy has become particularly useful not only for tissue diagnosis, but for treatment planning as well. Despite the widespread adoption of this useful tool, it is not without serious adverse sequelae, albeit rare. We present the first reported case of an acquired arteriovenous fistula (AVF) of the breast. A 34-year-old woman presented to the ColumbiaPresbyterian Comprehensive Medical Center with a 1-week history of breast discomfort. Three days prior to presenting to the center, the patient, a dialysis nurse, palpated a thrill on the medial aspect of her right breast. The patient had undergone an ultrasound-guided core biopsy of a 0.4 cm mass in the right breast 4 months earlier. At the end of the procedure, a marking clip was placed at the biopsy site (Fig. 1). The procedure was technically uneventful and was performed without incident. The patient remained asymptomatic until her presentation. She denied any history of recent trauma. Her past medical history was noncontributory, notable only for a strong family history of breast cancer. She had undergone a right breast excisional biopsy in 1998 that revealed fibrocystic changes. Clinical examination revealed symmetric breasts, without distortion or masses, and a palpable thrill over the medial aspect of her right breast at 3 o’clock. A bruit could be appreciated by auscultation. There was no breast or arm swelling on the

Free Silicone Injection Causing Polyarthropathy and Septic Shock

A 29-year-old man with transgender identity disorder presented with progressive, worsening pain in both breasts over a 2-week period. He had received breast “augmentation injections” as an inexpensive alternative to conventional augmentation mammaplasty. He was febrile and hypotensive. Both breasts had areas of erythema as well as multiple bullae. He also had bilateral tender, swollen ankles, knees, and wrists. Pathology from operative incision and drainage showed a florid histiocytic and giant cell response (Fig. 1A) and evidence of cellular response to infection (Fig. 1B). A magnetic resonance imaging (MRI) study was performed that showed multiple areas of foreign body in both breasts (Fig. 2). This necessitated return to the operating room for further debridement of the loculated abscesses. The polyarthropathy resolved completely with the resolution of the infectious process in the breasts. Local complications are well described in silicone gel extravasation from implant envelopes. Some described complications include extravasation of the gel transcutaneously, expression from the nipple, migration to the axillary lymph nodes, and even spread along tissue planes to the hand, causing a compartment syndrome-like phenomenon. In the diagnosis of silicone extravasation, there is no clear consensus as to the dominant study. Ultrasound, mammography, and MRI have all been favored by different studies. There is no controversy, however, that physical examination is inadequate in