Employment after a breast cancer diagnosis: a qualitative study of ethnically diverse urban women.

Employment status is related to treatment recovery and quality of life in breast cancer survivors, yet little is known about return to work in immigrant and minority survivors. We conducted an exploratory qualitative study using ethnically cohesive focus groups of urban breast cancer survivors who were African-American, African-Caribbean, Chinese, Filipina, Latina, or non-Latina white. We audio- and video-recorded, transcribed, and thematically coded the focus group discussions and we analyzed the coded transcripts within and across ethnic groups. Seven major themes emerged related to the participants' work experiences after diagnosis: normalcy, acceptance, identity, appearance, privacy, lack of flexibility at work, and employer support. Maintaining a sense of normalcy was cited as a benefit of working by survivors in each group. Acceptance of the cancer diagnosis was most common in the Chinese group and in participants who had a family history of breast cancer; those who described this attitude were likely to continue working throughout the treatment period. Appearance was important among all but the Chinese group and was related to privacy, which many thought was necessary to derive the benefit of normalcy at work. Employer support included schedule flexibility, medical confidentiality, and help maintaining a normal work environment, which was particularly important to our study sample. Overall, we found few differences between the different ethnic groups in our study. These results have important implications for the provision of support services to and clinical management of employed women with breast cancer, as well as for further large-scale research in disparities and employment outcomes.

Role of cytochrome c heme lyase in mitochondrial import and accumulation of cytochrome c in Saccharomyces cerevisiae.

Heme is covalently attached to cytochrome c by the enzyme cytochrome c heme lyase. To test whether heme attachment is required for import of cytochrome c into mitochondria in vivo, antibodies to cytochrome c have been used to assay the distributions of apo- and holocytochromes c in the cytoplasm and mitochondria from various strains of the yeast Saccharomyces cerevisiae. Strains lacking heme lyase accumulate apocytochrome c in the cytoplasm. Similar cytoplasmic accumulation is observed for an altered apocytochrome c in which serine residues were substituted for the two cysteine residues that normally serve as sites of heme attachment, even in the presence of normal levels of heme lyase. However, detectable amounts of this altered apocytochrome c are also found inside mitochondria. The level of internalized altered apocytochrome c is decreased in a strain that completely lacks heme lyase and is greatly increased in a strain that overexpresses heme lyase. Antibodies recognizing heme lyase were used to demonstrate that the enzyme is found on the outer surface of the inner mitochondrial membrane and is not enriched at sites of contact between the inner and outer mitochondrial membranes. These results suggest that apocytochrome c is transported across the outer mitochondrial membrane by a freely reversible process, binds to heme lyase in the intermembrane space, and is then trapped inside mitochondria by an irreversible conversion to holocytochrome c accompanied by folding to the native conformation. Altered apocytochrome c lacking the ability to have heme covalently attached accumulates in mitochondria only to the extent that it remains bound to heme lyase.

CYC2 encodes a factor involved in mitochondrial import of yeast cytochrome c.

The gene CYC2 from the yeast Saccharomyces cerevisiae was previously shown to affect levels of mitochondrial cytochrome c by acting at a posttranslational step in cytochrome c biosynthesis. We report here the cloning and identification of the CYC2 gene product as a protein involved in import of cytochrome c into mitochondria. CYC2 encodes a 168-amino-acid open reading frame with at least two potential transmembrane segments. Antibodies against a synthetic peptide corresponding to the carboxyl terminus of the predicted sequence were raised. These antibodies recognize multiple bands on immunoblots of mitochondrial extracts. The intensities of these bands vary according to the gene dosage of CYC2 in various isogenic strains. Immunoblotting of subcellular fractions suggests that the CYC2 gene product is a mitochondrial protein. Deletion of CYC2 leads to accumulation of apocytochrome c in the cytoplasm. However, strains with deletions of this gene still import low levels of cytochrome c into mitochondria. The effects of cyc2 mutations are more pronounced in rho- strains than in rho+ strains, even though rho- strains that are CYC2+ contain normal levels of holocytochrome c. cyc2 mutations affect levels of iso-1-cytochrome c more than they do levels of iso-2-cytochrome c, apparently because of the greater susceptibility of apo-iso-1-cytochrome c to degradation in the cytoplasm. We propose that CYC2 encodes a factor that increases the efficiency of cytochrome c import into mitochondria.

Lead neuropathy in adults and children.

All parts of the nervous systems can be affected, depending on the level and duration of exposure, by increased levels of lead. The occurrence of motor neuron disease, peripheral neuropathy, and encephalopathy are not mutually exclusive disorders for those individuals suffering from the toxic effects of lead. We present data that support the concept that increased absorption of lead produces changes in both central and peripheral nervous systems. Clinical and electrical evidence of subclinical involvement of peripheral nerves appears to be common to adults and children who are exposed to lead. These observations, accumulated from several possible sources of environmental hazard, also suggest that measurement of motor nerve conduction velocity may serve as an additional factor in the diagnosis of otherwise unrecognized toxic effects of lead.

Physician/patient-driven risk assignment in radiation oncology: reality or fancy?

PURPOSE: Treatment plan optimization in radiation oncology entails designing multiple x-ray beams to irradiate a tumor to a dose that will achieve locoregional control while minimizing normal tissue complications. For some anatomical sites, it is possible to estimate tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP) as a function of radiation dose. Thus, treatment plan optimization can be based on biologic end points rather than on dose calculations alone. Given multiple plans with different NTCPs and TCPs, a tradeoff must be made between maximizing TCP and maintaining an acceptable NTCP. How do physicians reach these decisions? Can the process be quantified? Should patients participate in the process? METHODS AND MATERIALS: Physicians and patients were asked to rank a series of treatment plans having different combinations of TCP and NTCP. Responses were parametrized into a figure of merit (FM) equation which quantifies predilections of TCP and NTCP. RESULTS: Physician-based FM equations are site- and patient-specific. Variations exist among physicians, but treatment plan selection is often conservative in accordance with the primum non nocere dictum. FM equations generated from the responses of patients suggest that some patients may be willing to accept higher treatment toxicity in exchange for increased TCP. CONCLUSION: The term "optimized treatment plan" contains inherently subjective criteria which reflect one's willingness to accept treatment morbidity in exchange for probability of cure. These criteria may differ among patients and/or physicians. A quantifiable FM may permit the design of custom-made treatment plans that include physician and patient input.

Pelvic exenteration for cervix cancer: would additional intraoperative interstitial brachytherapy improve survival?

OBJECTIVE: Improved local control with the addition of brachytherapy to pelvic exenteration for recurrent cervical cancer has been reported to improve survival. We examined the sites of recurrence after pelvic exenteration to determine if these patients might have been salvaged by the improved local control promised by interstitial brachytherapy. We sought to identify risk factors available intraoperatively or perioperatively which might predict decreased local control. METHODS: A retrospective review of 26 patients with recurrent cervical cancer who underwent total pelvic exenteration since 1988 at our institution was performed. RESULTS: Overall, the mean follow-up was 29.5 months (range 6.1-81.6). Of the 26 patients, 14 had no evidence of disease (NED), 1 was alive with disease (AWD), 9 were dead of disease (DOD), and 2 died of unrelated causes (DOC). Seven of 26 patients (27%) had margins < or = 5 mm, of whom 2 were NED, 4 DOD, and 1 AWD. Seven of 26 (27%) patients had lymphovascular involvement (LVI) or perineural invasion (PNI) with clear margins. Three of the seven with LVI or PNI and clear margins were NED, and four DOD. Of the 10 failures, 9 (90%) had close margins, PNI, or LVI. CONCLUSION: Our data reveal that 9 of 14 (64%) patients with close margins, LVI, or PNI were DOD or AWD, and 6 of 9 of those patients suffered local regional failure alone. Brachytherapy has the potential to cure 6 of 14 (43%) patients with these risk factors. Further study of brachytherapy at the time of pelvic extenteration is warranted.

Close or positive margins after surgical resection for the head and neck cancer patient: the addition of brachytherapy improves local control.

PURPOSE: Microscopically positive or close margins after surgical resection results in an approximately 21-26% local failure rate despite excellent postoperative external radiation therapy. We sought to demonstrate improved local control in head and neck cancer patients who had a resection with curative intent, and had unexpected, microscopically positive or close surgical margins. METHODS AND MATERIALS: Twenty-nine patients with microscopically close or positive margins after curative surgery were given definitive, adjuvant external radiation therapy and 125I brachytherapy. All 29 patients had squamous cell cancer and tonsil was the most common subsite within the head and neck region. After external radiation therapy and thorough discussions with the attending surgeon and pathologists, the slides, gross specimens, and appropriate radiographs were reviewed and a target volume was determined. The target volume was the region of the margin in question and varied in size based on the surgery and pathologic results. Once the target volume was identified the patient was taken back to the operating room for insertion of 125I seeds. Activity implanted (range 2.9-21.5 millicuries) was designed to administer a cumulative lifetime dose of 120-160 Gy. RESULTS: Twenty-nine patients were followed for a median of 26 months (range 5-86 months). Two-year actuarial local control was 92%. CONCLUSION: 125I, after external radiation therapy, is an excellent method to improve local control in the subset of patients with unexpectedly unsatisfactory margins.

Determination of size in invasive breast carcinoma: pathologic considerations and clinical implications.

The widespread use of mammography has made the detection of increasingly small, often impalpable, invasive breast carcinomas possible. An enhanced understanding of morphological factors, among the foremost of which is size of invasive component of carcinoma, is changing the management of breast cancer To the uninitiated, the determination of size of invasive component is seemingly simple but in practical terms is complicated by a number of ambiguous issues. Practical guidelines for the assessment of size of invasive carcinoma are proposed.

Partial Purification and Characterization of Three NAD(P)H Dehydrogenases from Beta vulgaris Mitochondria.

Mitochondria isolated from the taproot of beet (Beta vulgaris) were used in an effort to identify and partially purify the proteins constituting the exogenous NADH dehydrogenase. Three NAD(P)H dehydrogenases are released from these mitochondria by sonication, and these enzymes were partially purified using fast protein liquid chromatography. One of the enzymes, designated peak I, is capable of oxidizing NADPH and the beta form of NADH. The other two activities, peaks II and III, oxidize only beta-NADH. All three peaks are insensitive to divalent cation chelators and a complex I inhibitor, rotenone. The major component to peak I is a polypeptide with an apparent molecular mass of approximately 42 kilodaltons. Peak I activity was insensitive to platanetin, a specific inhibitor of the exogenous dehydrogenase, and insensitive to added Ca(2+) or Mg(2+). Peak I displayed a broad pH activity profile with an optimum between 7.5 and 8.0 for both NADPH and NADH. Purified peak II gave a single polypeptide of about 32 kilodaltons, had a pH optimum between 7.0 and 7.5, and was slightly stimulated by Ca(2+) and Mg(2+). As with peak I, platanetin had no effect on peak II activity. Peak III was not purified completely, but contained two major polypeptides with apparent molecular masses of 55 and 40 kilodaltons. This enzyme was not affected by Ca(2+) and Mg(2+), but was inhibited by platanetin. The peak III enzyme had a rather sharp pH optimum of approximately 6.5 to 6.6. The above data indicate that peak III activity is likely the exogenous NADH dehydrogenase.

Mitochondrial malate dehydrogenase from corn : purification of multiple forms.

A method to fractionate corn (Zea mays L. B73) mitochondria into soluble proteins, high molecular weight soluble proteins, and membrane proteins was developed. These fractions were analyzed by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and assays of mitochondrial enzyme activities. The Krebs cycle enzymes were enriched in the soluble fraction. Malate dehydrogenase has been purified from the soluble fraction by a two-step fast protein liquid chromatography method. Six different malate dehydrogenase peaks were obtained from the Mono Q column. These peaks were individually purified using a Phenyl Superose column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified peaks showed that three of the isoenzymes consisted of different homodimers (I, III, VI) and three were different heterodimers (II, IV, V). Apparent molecular masses of the three different monomer subunits were 37, 38, and 39 kilodaltons. Nondenaturing gel analysis of the malate dehydrogenase peaks showed that each Mono Q peak contained a band of malate dehydrogenase activity with different mobility. These observations are consistent with three nuclear genes encoding corn mitochondrial malate dehydrogenase. Polyclonal antibodies raised against purified malate dehydrogenase were used to identify the gene products using Western blots of two-dimensional gels.

Purification of maturation-promoting factor, an intracellular regulator of early mitotic events.

Maturation-promoting factor causes germinal vesicle breakdown when injected into Xenopus oocytes and can induce metaphase in a cell-free system. The cell-free assay was used to monitor maturation-promoting factor during its purification from unfertilized Xenopus eggs. Ammonium sulfate precipitation and six chromatographic procedures resulted in a preparation purified greater than 3000-fold that could induce germinal vesicle breakdown within 2 hr when injected into cycloheximide-treated oocytes. Proteins of 45 kDa and 32 kDa were correlated with fractions of highest activity in both assays. These fractions contained a protein kinase activity able to phosphorylate the endogenous 45-kDa protein, as well as histone H1, phosphatase inhibitor 1, and casein. The highly purified preparations described here should help to identify the mechanism of action of maturation-promoting factor and to elucidate the role of protein kinases in the induction of metaphase.

Mammographic findings after the removal of breast implants.

A recent wave of adverse publicity regarding silicone breast implants has led increasing numbers of women to undergo removal of their implants. In this pictorial essay, we present the spectrum of mammographic findings after implant removal. These range from a nearly normal appearance to architectural distortion and even residual spiculated silicone granulomas that may simulate malignant tumors. Our examples emphasize that comparison with previous mammograms and a detailed surgical history are essential if unnecessary investigations of postsurgical and residual benign abnormalities are to be avoided.

Mammographic positioning: evaluation from the view box.

To evaluate the quality of breast positioning for mediolateral oblique (MLO) and craniocaudal (CC) views, a prospective study of 1,000 consecutive bilateral screening mammographic examinations was performed. Six criteria were tested, including depth of tissue seen, inferior extent of the pectoral muscle relative to the posterior nipple line, presence of fibroglandular tissue at the posterior edge of the film, and whether the nipple was in profile. Pectoral muscle was depicted to within 1 cm of the nipple line or below it on 1,612 of the 2,000 MLO mammograms (81%); all fibroglandular tissue was depicted on 1,532 MLO mammograms (77%). The depth of tissue depicted on the CC mammogram was within 1 cm greater or less than the depth on the MLO mammogram on 1,586 CC mammograms (79%); the pectoral muscle was seen on 646 CC mammograms (32%). The nipple was in profile in 1,769 MLO mammograms (88%) and 1,783 CC mammograms (89%) but not in profile in either view in 83 cases (4%). Overall improvement was seen in 400 of 587 examinations (68%) when new mammograms were compared with previous mammograms. These criteria can be used to evaluate positioning performance and for quality control.

Mammographically guided fine-needle aspiration cytology of the breast: reducing the rate of insufficient specimens.

OBJECTIVE: The purpose of our study was to reduce the rate of insufficient specimens from fine-needle aspiration cytology (FNAC) of impalpable mammographically detected breast lesions. SUBJECTS AND METHODS: Our previous rate of insufficient specimens for FNAC was 27%. We implemented the following strategies to reduce this rate and improve accuracy: retraining of radiologists in FNAC procedures, more vigorous sampling, on-site evaluation of specimens by cytopathologist or cytotechnologist, exclusive use of stereotaxic guidance, stereotaxic equipment calibration program, and verification of initial needle placement. RESULTS: Of 77 patients with impalpable abnormalities who underwent FNAC with the new protocol, six (8%) had insufficient specimens for cytologic diagnosis: Four were incorrectly judged to contain sufficient material at the time of FNAC, one refused to complete the FNAC, and one had a vasovagal reaction. Of the six cases with insufficient specimens, four were benign at biopsy, one was malignant, and one was determined to be benign on the basis of mammographic stability. CONCLUSION: Modification of techniques and implementation of a quality assurance program can significantly improve the insufficient specimen rate for FNAC. Correlation of mammographic and cytologic findings also improves the management of these cases.

Increased risk of lung cancer after breast cancer radiation therapy in cigarette smokers.

BACKGROUND: Ionizing radiation is a lung carcinogen in a variety of settings, including after breast cancer radiation therapy. The authors explored whether cigarette smoking and breast cancer radiation therapy have a multiplicative effect on the risk of subsequent lung cancer. METHODS: This case-control study investigated women registered with primary breast cancer in the Connecticut Tumor Registry who developed a second malignancy between 1986 and 1989. Those diagnosed with a subsequent primary lung cancer were compared with those diagnosed with a subsequent nonsmoking, nonradiation-related second malignancy, and age-adjusted odds ratios were calculated with logistic regression. RESULTS: No radiation effects were observed within 10 years of initial primary breast cancer. Among both smokers and nonsmokers diagnosed with second primary cancers more than 10 years after an initial primary breast cancer, radiation therapy was associated with a 3-fold increased risk of lung cancer. A multiplicative effect was observed, with women exposed to both cigarette smoking and breast cancer radiation therapy having a relative risk of 32.7 (95% confidence interval [CI], 6.9-154). The radiation carcinogenic effect was observed only for the ipsilateral lung and not for the contralateral lung both in smokers and nonsmokers. CONCLUSIONS: Breast cancer radiation therapy, as delivered before 1980, increased the risk of lung cancer after ten years in nonsmokers, and a multiplicative effect was observed in smokers. For both smokers and nonsmokers, this effect was observed only for the ipsilateral lung and not the contralateral lung. Modern techniques, however, significantly decrease the radiation dose to the lungs, which may decrease the risk of lung cancer. Nonetheless, due to the available choices in early-stage breast cancer treatment, current practices may need to be revised for young breast cancer patients who smoke.

Silicone breast implants in vivo: MR imaging.

This study was designed to evaluate pulse sequences and patient positioning for MR imaging of silicone breast implants in patients. One hundred forty-three patients (281 silicone implants) underwent imaging over a 21-month period. The combination of a T2-weighted fast spin echo technique (SE), T2-weighted fast SE with water suppression, and T1-weighted SE with fat suppression is recommended to reliably differentiate silicone from other breast tissues and to identify intracapsular and extracapsular ruptures or leaks. Seventy of the 143 patients underwent removal of their silicone implants. The sensitivity for detection of silicone implant rupture was 76%, with a specificity of 97%. Positioning the patient prone improved image quality.