Microbial Diversity and Function in Shallow Subsurface Sediment and Oceanic Lithosphere of the Atlantis Massif.

The marine lithospheric subsurface is one of the largest biospheres on Earth; however, little is known about the identity and ecological function of microorganisms found in low abundance in this habitat, though these organisms impact global-scale biogeochemical cycling. Here, we describe the diversity and metabolic potential of sediment and endolithic (within rock) microbial communities found in ultrasmall amounts (101 to 104 cells cm-3) in the subsurface of the Atlantis Massif, an oceanic core complex on the Mid-Atlantic Ridge that was sampled on International Ocean Discovery Program (IODP) Expedition 357. This study used fluorescence-activated cell sorting (FACS) to enable the first amplicon, metagenomic, and single-cell genomic study of the shallow (<20 m below seafloor) subsurface of an actively serpentinizing marine system. The shallow subsurface biosphere of the Atlantis Massif was found to be distinct from communities observed in the nearby Lost City alkaline hydrothermal fluids and chimneys, yet similar to other low-temperature, aerobic subsurface settings. Genes associated with autotrophy were rare, although heterotrophy and aerobic carbon monoxide and formate cycling metabolisms were identified. Overall, this study reveals that the shallow subsurface of an oceanic core complex hosts a biosphere that is not fueled by active serpentinization reactions and by-products. IMPORTANCE The subsurface rock beneath the ocean is one of the largest biospheres on Earth, and microorganisms within influence global-scale nutrient cycles. This biosphere is difficult to study, in part due to the low concentrations of microorganisms that inhabit the vast volume of the marine lithosphere. In spite of the global significance of this biosphere, little is currently known about the microbial ecology of such rock-associated microorganisms. This study describes the identity and genomic potential of microorganisms in the subsurface rock and sediment at the Atlantis Massif, an underwater mountain near the Mid-Atlantic Ridge. To enable our analyses, fluorescence-activated cell sorting (FACS) was used as a means to concentrate cells from low biomass environmental samples for genomic analyses. We found distinct rock-associated microorganisms and found that the capacity for microorganisms to utilize organic carbon was the most prevalent form of carbon cycling. We additionally identified a potential role for carbon monoxide metabolism in the subsurface.

Dual-energy CT in patients with abdominal malignant lymphoma: impact of noise-optimised virtual monoenergetic imaging on objective and subjective image quality.

AIM: To investigate the impact of noise-optimised virtual monoenergetic imaging (VMI+) reconstructions on quantitative and qualitative image parameters in patients with malignant lymphoma at dual-energy computed tomography (DECT) examinations of the abdomen. MATERIALS AND METHODS: Thirty-five consecutive patients (mean age, 53.8±18.6 years; range, 21-82 years) with histologically proven malignant lymphoma of the abdomen were included retrospectively. Images were post-processed with standard linear blending (M_0.6), traditional VMI, and VMI+ technique at energy levels ranging from 40 to 100 keV in 10 keV increments. Signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were objectively measured in lymphoma lesions. Image quality, lesion delineation, and image noise were rated subjectively by three blinded observers using five-point Likert scales. RESULTS: Quantitative image quality parameters peaked at 40-keV VMI+ (SNR, 15.77±7.74; CNR, 18.27±8.04) with significant differences compared to standard linearly blended M_0.6 (SNR, 7.96±3.26; CNR, 13.55±3.47) and all traditional VMI series (p<0.001). Qualitative image quality assessment revealed significantly superior ratings for image quality at 60-keV VMI+ (median, 5) in comparison with all other image series (p<0.001). Assessment of lesion delineation showed the highest rating scores for 40-keV VMI+ series (median, 5), while lowest subjective image noise was found for 100-keV VMI+ reconstructions (median, 5). CONCLUSION: Low-keV VMI+ reconstructions led to improved image quality and lesion delineation of malignant lymphoma lesions compared to standard image reconstruction and traditional VMI at abdominal DECT examinations.

Dual-energy CT with iodine quantification in distinguishing between bland and neoplastic portal vein thrombosis in patients with hepatocellular carcinoma.

AIM: To investigate the diagnostic accuracy of dual-energy multidetector computed tomography (MDCT) with iodine quantification compared to conventional enhancement measurements in distinguishing bland from neoplastic portal vein thrombosis in patients with hepatocellular carcinoma. MATERIAL AND METHODS: Thirty-four patients (26 men, eight women; mean age, 62 years) with hepatocellular carcinoma and portal vein thrombosis underwent contrast-enhanced dual-energy MDCT during the late hepatic arterial phase for the assessment of portal thrombosis (bland, n=21; neoplastic, n=13). Datasets were analysed separately by two different readers. Interobserver correlation and variability were calculated and compared with the Bland-Altman method. Diagnostic accuracy of conventional enhancement measurements and iodine quantification was calculated by setting either histopathology (n=7) or a reference standard based on MDCT imaging criteria and thrombus evolutionary characteristics compared to a previous MDCT examination (n=27). For iodine quantification threshold determination receiver operating characteristic (ROC) curves were drawn. p-Values <0.05 were considered significant. RESULTS: For conventional enhancement measurements and iodine quantification interobserver correlation was 98% and 96%. Enhancement measurement resulted in a sensitivity of 92.3%, specificity of 85.7%, positive predictive value (PPV) of 80%, and negative predictive value (NPV) of 94.7%. An iodine concentration of 0.9 mg/ml optimised discrimination between neoplastic and bland thrombi (area under the ROC [AUC] 0.993) resulting in a sensitivity of 100%, specificity of 95.2%, PPV of 92.9%, and NPV of 100%. The overall diagnostic accuracy of iodine quantification (97%) was significantly better than conventional enhancement measurements (88.2%; p<0.001). CONCLUSION: Compared to conventional enhancement measurements, iodine quantification improves the characterisation of portal vein thrombi during the late hepatic arterial phase in patients with hepatocellular carcinoma.

Increasing hepatitis B vaccination coverage among healthcare workers in Italy 10 years apart.

BACKGROUND: In Italy, vaccination against hepatitis B virus infection was strongly recommended for healthcare workers since 1985. Update findings on vaccination coverage are lacking. AIM: To assess current vaccination coverage against hepatitis B in this job category. METHODS: In 2006, 1,632 healthcare workers randomly selected in 15 Italian public hospitals completed a self-administered precoded questionnaire. RESULTS: The overall vaccination coverage was 85.3%, a figure higher than the 64.5% observed in 1996. Vaccine coverage showed a significant downtrend (p<0.01) from the Northern (93.1%) to the Southern (77.7%) areas. Logistic regression analysis showed that residence in the North (Odds ratio 4.2; 95% confidence interval 2.6-6.7) and youngest age (Odds ratio 4.5; 95% confidence interval 2.6-7.8), both were independent predictors of vaccine acceptance. CONCLUSIONS: Ten years apart, vaccine coverage has markedly increased, closely paralleling the downtrend in the incidence of acute B hepatitis among healthcare workers in Italy.

Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer.

BACKGROUND: Breast-conservation therapy for early-stage breast cancer is now an accepted treatment, but there is still controversy about its comparability with mastectomy. Between 1979 and 1987, the National Cancer Institute conducted a randomized, single-institution trial comparing lumpectomy, axillary dissection, and radiation with mastectomy and axillary dissection for stage I and II breast cancer. We update the results of that trial after a median potential follow-up of 10.1 years. METHODS: Two hundred forty-seven patients with clinical stage I and II breast cancer were randomly assigned to undergo either modified radical mastectomy or lumpectomy, axillary dissection, and radiation therapy. The 237 patients who actually underwent randomization have been followed for a median of 10.1 years. The primary end points were overall survival and disease-free survival. RESULTS: At 10 years overall survival was 75 percent for the patients assigned to mastectomy and 77 percent for those assigned to lumpectomy plus radiation (P = 0.89). Disease-free survival at 10 years was 69 percent for the patients assigned to mastectomy and 72 percent for those assigned to lumpectomy plus radiation (P = 0.93). The rate of local regional recurrence at 10 years was 10 percent after mastectomy and 5 percent after lumpectomy plus radiation (P = 0.17) after recurrences successfully treated by mastectomy were censored from the analysis. CONCLUSIONS: In the management of stage I and II breast cancer, breast conservation with lumpectomy and radiation offers results at 10 years that are equivalent to those with mastectomy.

Mastectomy versus conservative surgery and radiation therapy. Psychosocial consequences.

BACKGROUND: Clinical trials comparing mastectomy to conservative surgery plus radiation therapy in the treatment of breast cancer have provided an opportunity to increase understanding of the biology of this disease and the psychological adaptation of the breast cancer patient. Because these local treatments appear to be equal in terms of survival, the question remains as to whether conservative surgery plus radiation therapy confers a measure of psychological comfort superior to that of mastectomy for women diagnosed with early-stage breast cancer. METHODS: One hundred forty-two women participating in a clinical trial randomizing patients to mastectomy or lumpectomy and radiation therapy were prospectively evaluated for psychological response to their respective local therapy. A baseline assessment before randomization and subsequent questionnaires at 6, 12, and 24 months after treatment were completed by patients entered in the clinical trial. RESULTS: At 6 months, mastectomy patients reported significantly less control over events in their lives (P = 0.003) and more problems with sexual relations (P = 0.021) than did their conservatively treated counterparts. In addition, there were marked differences between mastectomy patients and lumpectomy and radiation therapy patients in the degree of distress over their nude bodies, with P = 0.001 at 6 months, P = 0.019 at 12 months, and P = 0.057 at 24 months. CONCLUSIONS: From our findings, it appears that breast conservation therapy protects women's perception of their body but does not, over time, contribute to a more positive sexual adjustment.

Is c-erb B-2 a predictor for recurrent disease in early stage breast cancer?

PURPOSE: To assess the prognostic importance of c-erb B-2 expression in early stage breast cancer. METHODS AND MATERIALS: Immunohistochemical analysis for c-erb B-2 over-expression was retrospectively performed on 107 paraffin-embedded specimens of women with Stage I or II breast cancer entered in a randomized trial. Results were correlated with known prognostic factors such as pathologic axillary involvement, T-size, estrogen and progesterone receptor status, and nuclear grade. Immunohistochemical staining for c-erb B-2 protein expression was also correlated with breast/chest wall failure as well as survival without evidence of disease (NED) and overall survival. RESULTS: C-erb B-2 overexpression was positive in 21% of the biopsy specimens. A significant association was found between c-erb-2 positivity and lesions containing an intraductal component, with 62% of lesions staining positively for c-erb B-2 having an intraductal component compared to only 36% of lesions with an intraductal component staining negatively for the c-erb B-2 protein (p2 = .031). A significant correlation between c-erb B-2 protein over-expression and axillary nodal status, primary tumor size, nuclear grade, and estrogen and progesterone receptor status was not identified. Cox proportional hazards model did not show a significant effect of c-erb B-2 expression for NED or overall survival. CONCLUSION: Our study did not find over-expression of c-erb B-2 to reliably predict for recurrent disease in early stage breast cancer. This data can be added to other series comparing erb B-2 expression and disease outcome among node-positive and node-negative women with carcinoma of the breast.

A pilot study of pi-class glutathione S-transferase expression in breast cancer: correlation with estrogen receptor expression and prognosis in node-negative breast cancer.

PURPOSE AND METHODS: Previous studies have indicated that RNA levels for pi-class glutathione S-transferase (GST pi), a phase II, drug-metabolizing enzyme, were inversely related to estrogen receptor (ER) and progesterone receptor (PR) levels in human breast tumors. Because GST pi also is expressed in normal breast epithelium, an immunohistochemical assay that uses affinity-purified polyclonal antibodies to GST pi was developed to examine the possible relationship between GST pi expression in breast cancer cells and hormone receptor expression, as well as prognosis, in patients with primary breast cancer. RESULTS: A strong inverse correlation between GST pi expression and ER (two-sided P [P2] = .002) and PR status (P2 = .023) was found in our study of 189 patients with primary breast cancer. GST pi expression was not related to tumor size, nodal metastasis, nuclear grade, histology, or age of the patient. In node-negative breast cancer (n = 72), increased GST pi expression was associated with decreased disease-free survival (DFS) and overall survival (OS). When GST pi expression was divided into categories of negative (no GST pi-positive tumor cells), intermediate (1% to 70% GST pi-positive tumor cells), and high (> 70% GST pi-positive tumor cells), the relative risk of tumor recurrence in patients with node-negative breast cancer was increased 3.39-fold for each successive category of expression (P2 = .0045; 95% confidence interval, 1.46 to 7.87) and the relative risk of death was increased 4.49-fold for each successive category (P2 = .0003; 95% confidence interval, 2.02 to 10.42). The actuarial 5-year OS was 100%, 79%, and 51%, and the DFS was 94%, 77%, and 44%, for the negative, intermediate, and high tumor groups, respectively. Among the factors studied in multivariate analysis (ER status, PR status, nuclear grade, and tumor size), GST pi expression was the factor that most accurately predicted shorter DFS and OS in node-negative patients. CONCLUSION: GST pi expression is inversely related to hormone receptor status in breast cancer. This pilot study also suggests that increased GST pi expression may be an important predictor of early recurrence and death in node-negative breast cancer patients that merits additional investigation.

Mastectomy versus breast-conserving therapy in the treatment of stage I and II carcinoma of the breast: a randomized trial at the National Cancer Institute.

PURPOSE: Mastectomy versus excisional biopsy (lumpectomy) plus radiation for the treatment of stage I and II breast cancer was compared in a prospective randomized study. PATIENTS AND METHODS: From 1979 to 1987, 247 women were randomized and 237 were treated on this study. All patients received a full axillary dissection and all node-positive patients received adjuvant chemotherapy with cyclophosphamide and doxorubicin. Radiation consisted of external-beam therapy to the whole breast with or without supraclavicular nodal irradiation followed by a boost to the tumor bed. RESULTS: The minimum time on the study was 18 months and the median time on the study was 68 months. No differences in overall survival or disease-free survival were observed. Actuarial estimates at 5 years showed that 85% of mastectomy-treated patients were alive compared with 89% of the lumpectomy/radiation patients (P2 = .49; 95% two-sided confidence interval [CI] about this difference, 0% to 9% favoring lumpectomy plus radiation). The probability of failure in the irradiated breast was 12% by 5 years and 20% by 8 years according to actuarial estimates. Of 15 local breast failures, 14 were treated with and 12 were controlled by mastectomy; the ultimate local-regional control was similar in both arms of the trial. CONCLUSION: These data add further weight to the conclusion that breast conservation using lumpectomy and breast irradiation is equivalent to mastectomy in terms of survival and ultimate local control for stage I and II breast cancer patients.

Results of the National Cancer Institute early breast cancer trial.

In 1979, a prospective, randomized trial was begun at the National Cancer Institute comparing lumpectomy, axillary dissection, and radiation therapy (XRT) to modified radical mastectomy for the treatment of invasive breast cancer, clinical stage T1-2, N0-1, M0. Treatment in the radiation arm consisted of full axillary dissection and gross removal of the tumor, followed by 4500 to 5000 cGy to the whole breast and a boost to the tumor bed of 1500 to 2000 cGy. Patients with positive axillary dissections received radiation to the supraclavicular nodes, in addition to cyclophosphamide and doxorubicin. Two hundred thirty-seven patients entered in the trial between 1979 and 1987 are available for analysis, 116 in the mastectomy arm and 121 in the radiation arm. With a median follow-up of 67.7 months, there are no significant differences in 5-year overall survival (85% vs 89%, mastectomy vs radiation) or 5-year disease-free survival (82% vs 72%, mastectomy vs radiation). Patients in the radiation arm had an actuarial in-breast recurrence rate of 12% at 5 years and 20% at 8 years. There were no major differences between complication rates in the treatment arms. The results of the study indicate that patients with invasive breast cancer, stage I and II, can be treated with lumpectomy, axillary dissection, and radiation therapy with results comparable to those with modified radical mastectomy.

Comparison of pain, motion, and edema after modified radical mastectomy vs. local excision with axillary dissection and radiation.

Recent data suggest that prognosis is similar for women with primary breast cancer whether they receive modified radical mastectomy (MRM) or local excision and axillary dissection with radiation (XRT). The effects of either of these treatments on arm mobility, pain, or edema have not been compared. To assess the impact of MRM or XRT on mobility, pain, or edema, we evaluated patients treated in a prospective randomized trial designed to assess prognosis following MRM or XRT. All were provided a standardized physical therapy program including arm mobilization, shoulder strengthening, prevention and treatment of upper extremity edema, and education about arm function. Patients were evaluated for chest wall pain, arm motion, muscle strength, and edema as determined by circumferential measurements at the wrist, forearm, and arm. Evaluations were performed preoperatively and at yearly anniversaries of their surgery. Women receiving XRT had more chest wall tenderness at 1 and 2 years after surgery than those receiving MRM (p2 less than 0.0001 and p2 = 0.0007 respectively). Those receiving MRM were slower to reach their preoperative range of motion (ROM) (p2 = 0.043). Incidence of muscle weakness was similar in both groups. The few patients with local recurrence of tumor had more upper extremity edema than those who did not recur (p2 = 0.085) at 1 year and (p2 = 0.02) at 2 years. In patients who did not develop local recurrence, those who had received XRT had greater but nonsignificant increases in upper extremity circumferential measures compared with those receiving MRM at any anniversary evaluation. Patients receiving MRM and XRT are likely to have some differences in functional outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Level of axillary involvement by lymph node metastases from breast cancer is not an independent predictor of survival.

We examined the relationship of axillary level of lymph node metastases from clinical stage I and II breast cancer to overall survival and disease-free survival rates in 135 patients who underwent complete axillary lymph node dissection to determine if anatomic level of axillary involvement (I vs II vs III) is an independent prognostic factor. All patients underwent either modified radical mastectomy or lumpectomy with axillary dissection and whole breast radiotherapy for breast cancer. Median follow-up was 6.9 years. We found no difference in overall survival or disease-free survival between patients whose highest or only level of axillary involvement was level I compared with patients whose highest or only level was II. Although patients whose highest level of nodal involvement was III had significantly worse overall survival and disease-free survival rates than patients whose highest nodal involvement was I or II, when patients were stratified by the total number of positive nodes (one to three vs four or more), there was no difference in overall survival or disease-free survival rates between levels I, II, and III. These findings indicate that the level of axillary involvement for stage II breast cancer is not of independent prognostic significance.

Immunological and psychosocial predictors of disease recurrence in patients with early-stage breast cancer.

Ninety women with recently diagnosed stage I or stage II breast cancer who had been admitted to the NIH Clinical Center and were participating in a randomized trial were entered onto this behavioral immunology protocol. Patients were immunologically and psychosocially assessed at baseline (approximately 5 days after surgery) and again at 3 and 15 months post surgery. All of the patients were followed up for a minimum of 5 years, and 60% of the patients were followed for 7 years or longer. Twenty-nine women in the study group reported disease recurrences over the entire follow-up period. Causal path modeling statistical techniques showed that natural killer (NK) cell activity was a strong predictor of disease outcome when the outcome variable was defined as recurrence v nonrecurrence of disease (chi 2 = 6.9, p less than .001). Higher NK cell activity at follow-up predicted disease-free survival over the follow-up period. When the disease outcome variable was operationally defined as time to recurrent disease, the psychosocial factors were more strongly predictive of the rate of disease progression for those who had a recurrence (chi 2 = -4.1, p less than .01), but NK cell activity was seemingly less relevant in this latter case. Overall, these findings suggest that including mood and potentially relevant immunological variables, along with important biological prognostic variables, in multivariate and prospective models such as those examined in this study, potentially contributes more to the explanation of greater outcome variance of early-stage breast cancer than has been believed in the past.

Breast conservation versus mastectomy: distress sequelae as a function of choice.

Between 1981 and 1984, 93 stage I and II breast cancer patients were entered onto a trial at the National Cancer Institute (NCI) randomizing patients to excisional biopsy plus radiation v mastectomy. Between 1984 and 1987, 98 stage I and II breast cancer patients were entered onto a behavioral study in Pittsburgh, approximately 70% of whom elected to have breast conservation surgery. Patients at both sites were assessed three to five days postsurgery, and again at 3-month's follow-up, using a well-validated mood measure, the Profile of Mood States (POMS). There were no demographic or disease differences between the two samples. In the Pittsburgh sample, using a repeated measures multivariate analysis of covariance (MANCOVA) analysis, after adjusting for menopausal status and radiotherapy and chemotherapy toxicity, the conservation group was psychologically worse off (F = 2.7, P less than .03). For example, they were significantly more distressed over time (F = 5.5, P less than .02), and more depressed in general (F = 9.2, P less than .005). Using Karnofsky ratings, the two groups were identical in terms of disability at 3-month's follow-up. In contrast, for the NCI patients participating in the randomized trial, after adjusting for chemotherapy and radiotherapy treatments, reported overall distress decreased over time (F = 17.4, P less than .0001) for all patients, irrespective of treatment group, and the between-groups MANCOVA was not significant. Thus, when comparing the two samples, when "choice" played a major role, the conservation patients were psychologically worse off--at least at 3-month's follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast reconstruction using tissue expanders.

Breast reconstruction options are available to virtually all women undergoing mastectomy. Breast reconstruction may increase the woman's self-esteem and foster a more positive body image. Tissue expansion provides a means of developing breast symmetry with minimal surgical intervention. It can be used when the skin and soft tissue remaining after mastectomy are of good quality but inadequate quantity. The nurse's role encompasses physical and psychological support and patient education.

Correlation of stress factors with sustained depression of natural killer cell activity and predicted prognosis in patients with breast cancer.

Natural killer (NK) cell activity and psychological status were measured at baseline and at 3 months into treatment, as part of the National Cancer Institute (NCI) Protocol 79-C-111, randomizing breast cancer patients to lumpectomy/radiation v mastectomy. Patients who were found to have positive axillary lymph nodes also received combination chemotherapy (Adriamycin [Adria Laboratories, Columbus, OH], plus Cytoxan [Mead Johnson Pharmaceuticals, Evansville, IN] or methotrexate, plus 5-fluorouracil [5-FU]). Seventy-five patients were entered onto this behavioral immunology protocol at the time of data analysis. We reported in an earlier publication that NK activity was an important predictor of patient baseline prognosis relevant to nodal status. In that study, by using multiple regression analyses, 51% of the baseline NK activity variance could be accounted for by entering three distress indicators into the equation (patient "adjustment," lack of social support, and fatigue/depression symptoms). On reassessment of NK activity after 3 months, it was found that NK activity was not affected by the interim administration of chemotherapy and/or radiotherapy. However, consistent with our earlier findings, NK activity levels remained markedly lower in patients with positive nodes than in patients with negative nodes (at 60 to 1 effector to target cell [E:T] ratio, mean of 18% lytic activity v mean of 31% lytic activity [t = 1.87, P less than .05]). Even though average levels of NK activity were lower for patients with more tumor burden, there was still a substantial range of NK activity levels within the node positive patient group, as well as within the patient group as a whole. We hypothesized that differences in levels of NK activity could be predicted on the basis of baseline distress factors found to be significant in our earlier report. In fact, we found that we could account for 30% of NK activity level variance at 3 months follow-up on the basis of baseline NK activity, fatigue/depression, and lack of social support. Therefore, although neither radiation nor chemotherapy appeared to affect NK activity, tumor burden was again clearly associated with NK activity levels, and a significant amount of baseline and 3-month NK activity could be predicted on the basis of CNS-mediated effects. At the least, such factors provide a psychological marker of host biological status.

Complete axillary lymph node dissection for stage I-II carcinoma of the breast.

We reviewed the complete axillary dissection specimens of 136 patients with stage I-II breast cancer to clarify the distribution of axillary lymph node metastases in this disease. Our series included 71 patients undergoing axillary dissection as part of a modified radical mastectomy (MRM) and 65 patients undergoing axillary dissection in conjunction with conservative surgery of the breast and definitive postoperative breast radiotherapy (CAD). These two groups of patients were comparable according to age, menopausal status, tumor size, and clinical stage. In all patients the pectoralis minor muscle was excised and all axillary tissue removed. Each specimen contained a median of 23 lymph nodes. The axillary levels (I, II, III) were determined according to the relationship of axillary tissue to the pectoralis minor muscle (lateral, inferior, medial). Thirty-nine percent of the lymph nodes were contained in level I, 41% in level II, and 20% in level III. There were no significant differences noted in the number of lymph nodes or in the distribution of lymph nodes according to axillary level between dissections performed as part of the MRM or those done as a single procedure (CAD). Sixty-five patients (47.8%) had one or more positive lymph nodes in their axillary specimen. The clinical and pathologic stage was determined and compared for all patients. Among patients judged to have a clinically negative axilla, 37.6% had histologically positive lymph nodes (clinical false-negative rate). For patients with a clinically positive axilla, 11.1% had, histologically, no evidence of metastatic disease (clinical false-positive rate). When the distribution of lymph node metastases according to axillary level was studied, it was found that 29.2% of lymph node-positive patients (or 14.0% of all patients) had metastases only to level II and/or III of the axilla, with level I being negative (skip metastases). This incidence of skip metastases was greater among clinically node-negative than among clinically node-positive patients, but was not related to the size or location of the primary tumor in the breast. In addition, it was found that 20.0% of lymph node-positive patients (or 9.6% of all patients) were converted from three or fewer to four or more positive nodes by analysis of lymph nodes contained in levels II and III. This conversion from three or fewer to four or more positive nodes was due primarily to information contained in level II, with level III contributing to a smaller degree.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of definitive radiation therapy for primary breast cancer on ability to deliver adjuvant chemotherapy.

Primary radiotherapy as a means of managing stage I and II breast cancer is receiving increasing attention. In a prospectively randomized trial comparing modified radical mastectomy to lumpectomy followed by definitive radiotherapy, we evaluated whether radiotherapy has a deleterious effect on the ability to administer adjuvant doxorubicin and cyclophosphamide to patients with histologically positive axillary lymph nodes. All patients were treated with an identical regimen, and doses were escalated to the same degree until myelosuppression occurred. There were no significant differences in the amount of chemotherapy administered to either treatment group. Patients in both groups received approximately 100% of the predicted dose of doxorubicin and approximately 117% of the predicted dose of cyclophosphamide. At present, we have no evidence that there are differences in recurrence rates as a function of the quantity of drug received, although longer follow-up is required.