Mammary Paget's disease and radiotherapy: a systematic literature review.

OBJECTIVE: Paget disease of the breast (PDB) is a rare form of cutaneous breast cancer. Up to date, no randomized studies evaluated the different management strategies. This systematic review investigates the role of radiotherapy and its best technical profile in the treatment of this disease, with great attention to doses and fractionation regimens. MATERIALS AND METHODS: A systematic search was performed on PubMed, Embase and Scopus in order to detect case reports, case series and prospective as well as retrospective clinical studies describing histologically proven PDB and providing information about pertinent radiation treatments. Searching strategy followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. RESULTS: Inclusion criteria were met by six papers, dealing with radiation treatments performed postoperatively and in exclusive settings. No evaluations were performed on preoperative radiotherapy. CONCLUSIONS: Actually, the standard treatment of PDB reflects oncological principles of breast carcinoma therapy, including the role of breast-preserving surgery. The traditional radiotherapic dose is 50 Gy, with daily fractionation of 2 Gy. Adjuvant radiotherapy following breast preserving surgery represents the current standard of care; prospective studies could be of help in defining the role of exclusive radiotherapy, hypofractionated schemes and smaller target volumes.

Ovulation and fertility response to commercially available GnRH products in lactating cows synchronized with the Double-Ovsynch protocol.

This study was designed to evaluate whether commonly used gonadorelin products that are commercially available in the United States results in comparable ovulation and pregnancy per AI (P/AI) in synchronized lactating dairy cows. A total of 1411 Holstein cows receiving a Double-Ovsynch protocol (DOV) for conducting the first postpartum AI were randomized to receive one of the following GnRH products throughout the Double-Ovsynch: 1) Cystorelin® (CYS, gonadorelin diacetate tetrahydrate, n = 484); 2) Factrel® (FAC, gonadorelin hydrochloride, n = 482) or; 3) Fertagyl® (FER, gonadorelin diacetate tetrahydrate, n = 515). A subgroup of cows (n = 487) received ovarian ultrasound exams and collection of blood samples for progesterone (P4) analysis. Proportion of cows ovulating following the 3rd GnRH of DOV tended (P = 0.07) to differ between GnRH salts (hydrochloride = 61.5% vs. diacetate = 72.7%) but was similar for GnRH products (FER = 74.1% vs. FAC = 61.5% vs. CYS = 72.2%). Interestingly, a logistic regression analyses that considered the circulating P4 at the time of GnRH treatment indicated lower ovulation responses to FAC compared to FER and CYS; although greater circulating P4 decreased ovulation response to all GnRH products. Results for P/AI at 60 d post-insemination differed between GnRH salts (P = 0.02) as well as GnRH products (FER = 47.8% vs. FAC = 42.0% vs. CYS = 49.8%; P = 0.04). In conclusion, fertility following use of the Double-Ovsynch was less following a hydrochloride-based GnRH product likely due to lesser ovulatory responses throughout the synchronization protocol.

Economic feasibility of cooling dry cows across the United States.

Heat stress during the dry period reduces milk yield in the subsequent lactation of dairy cows. Our objectives were to quantify the economic losses due to heat stress if dry cows are not cooled and to evaluate the economic feasibility of dry cow cooling. We used weather data from the National Oceanic and Atmospheric Administration to calculate the number of heat stress days for each of the 50 US states. A heat stress day was declared when the daily average temperature-humidity index was ≥68. The number of dairy cows in each state in 2015 was obtained from the USDA-National Agricultural Statistics Service. We assumed that 15% of the cows were dry at any time, a 60-d dry period, and a calving interval of 400d. Only cows in their second or greater parity (65%) benefitted from cooling during the dry period of the previous parity. Milk yield decreased by 5kg in the subsequent lactation (340d) if the cow experienced heat stress during the dry period based on a review of the literature. The default marginal value of milk minus feed cost was $0.33/kg of milk. The investment analysis included purchases of fans and soakers and use of water and electricity. Investment in a dry cow barn was considered separately. The average US dairy cow would experience 96 (26%) heat stress days during the year if not cooled and loses 447kg of milk in the subsequent lactation if not cooled when dry. Annual losses would be $810 million if dry cows were not cooled ($87/cow per yr). For the top 3 milk-producing states (California, Wisconsin, New York), and Florida and Texas, the average milk losses in the subsequent lactation were 522, 349, 387, 1,197, and 904kg, and reduced profit per cow per year would be $101, $68, $75, $233, and $176, respectively. The average benefit-cost ratio and payback periods of cooling dry cows in the United States were 3.15 and 0.27 yr (dry cow barn already present) and 1.45 and 5.68 yr (if investing in a dry cow barn) in the default scenario. To reach positive net present values, 6d (barn is present) and 55d (barn investment necessary) of heat stress annually were necessary (default assumptions). Other benefits of cooling, such as increased health and more productive offspring, were not considered. In conclusion, cooling of dry cows was profitable for 89% of the cows in the United States when building a new barn is required (under default assumptions) and very profitable when construction of a dry cow barn is not required (except for Alaska).

Fat grafting for breast cancer patients: From basic science to clinical studies.

Fat grafting in the surgical treatment of breast cancer has become popular in a short period of time because of the rising expectations of good esthetic results by the patients as well as the simplicity of the technique; however, the oncological safety for breast cancer patients remains a matter of debate. The procedure raises many questions considering that recent in-vitro studies have shown that fat grafting could promote tumor recurrence through diverse mechanisms, or even facilitate distant metastasis. We present a review of the currently available experimental and clinical data in order to describe and discuss patient selection criteria following breast cancer surgery.

Physiologic, health, and production responses of dairy cows supplemented with an immunomodulatory feed ingredient during the transition period.

This study compared physiological, health, and productive parameters in dairy cows supplemented or not with Omnigen-AF (OMN; Phibro Animal Health, Teaneck, NJ) during the transition period. Thirty-eight nonlactating, multiparous, pregnant Holstein × Gir cows were ranked by body weight (BW) and body condition score (BCS), and assigned to receive (n=19) or not (CON; n=19) OMN at 56 g/cow daily (as-fed basis) beginning 35 d before expected date of calving. Before calving, cows were maintained in single drylot pen with ad libitum access to corn silage, and received (as-fed basis) 3kg/cow daily of a concentrate. After calving, cows were moved to an adjacent drylot pen, milked twice daily, offered (as-fed basis) 35kg/cow daily of corn silage, and individually received a concentrate formulated to meet their nutritional requirements after both milkings. Cows received OMN individually as top-dressing in the morning concentrate feeding. Before calving, cow BW and BCS were recorded weekly and blood samples were collected every 5 d beginning on d -35 relative to expected calving date. After calving and until 46 d in milk, BW and BCS were recorded weekly, individual milk production was recorded, and milk samples were collected daily for total solids and somatic cell count analyses. Blood was sampled daily from 0 to 7 d in milk, every other day from 9 to 21 d in milk, and every 5 d from 26 to 46 d in milk. On 30 and 46 d in milk, cows were evaluated for endometritis via cytobrush technique, based on % of polymorphonuclear (PMN) cells in 100 total cell count (PMN + endometrial cells). On 48.7±1.6 d in milk, 9 cows/treatment received a lipopolysaccharide (LPS) injection (0.25µg/kg of BW), and blood was sampled hourly from -2 to 8 h, at 12-h intervals from 12 to 72 h, and at 24-h intervals form 96 to 120 h relative to LPS administration. No treatment differences were detected on BW, BCS, serum concentrations of cortisol, fatty acids, insulin, glucose, haptoglobin, cortisol, and insulin-like growth factor-I. Cows receiving OMN had greater milk yield (30.3 vs. 27.1kg/d) and percentage of PMN cells in endometrial cell population (12.2 vs. 3.9%) compared with CON cows. After LPS administration, cows receiving OMN had greater mean serum haptoglobin (212 vs. 94 µg/mL), as well as greater serum concentration of tumor necrosis factor α at 1, 2, and 3 h relative to LPS injection compared with CON cows. In conclusion, OMN supplementation during the transition period enhanced innate immunity parameters and increased milk production in dairy cows.

Effects of excessive energy intake and supplementation with chromium propionate on insulin resistance parameters in nonlactating dairy cows.

The objective was to compare insulin resistance parameters in cows with adequate or excessive energy intake as well as in cows with excessive energy intake receiving Cr supplementation as chromium propionate. Thirteen multiparous, nonlactating Gir × Holstein cows were ranked by BW and BCS and assigned to 1 of 3 dietary treatments on d 0: 1) diet to meet their ME requirements without Cr supplementation (MAN; n = 4), 2) diet to exceed their ME requirements without Cr supplementation (HIGH; n = 4), and 3) HIGH with 2.5 g/d of chromium propionate (HIGHCR; n = 5, with 10 mg of Cr/cow daily). Diets were formulated to provide 100% of daily ME requirements of MAN and 177% of daily ME requirements of HIGH and HIGHCR cows and offered twice daily via individual self-locking head gates from d 0 to 88. Cow BW and BCS were recorded on d 0 and 88 of the experiment. Blood samples were collected before and 2 h after the morning feeding twice weekly. Preprandial revised quantitative insulin sensitivity check index (RQUICKI) was determined using serum glucose, insulin, and NEFA concentrations obtained before feeding. Glucose tolerance tests (GTT) were performed on d 32 and 88 by infusing cows with 0.5 g of glucose/kg of BW whereas blood samples were collected at -15, 0, 10, 20, 30, 45, 60, and 90 min relative to infusion. Change in BCS tended to be greater in HIGH and HIGHCR (P = 0.09) compared with MAN cows. Within samples collected twice weekly, serum concentrations of glucose, insulin (beginning on d 14 of the experiment), and NEFA (preprandial samples only) were greater (P ≤ 0.05) in HIGH compared with HIGHCR cows and tended to be greater in HIGH compared with MAN cows (P ≤ 0.10) but did not differ (P ≥ 0.52) between HIGHCR and MAN cows. Moreover, HIGH cows had reduced RQUICKI compared with MAN (P = 0.02) and HIGHCR cows (P = 0.05) whereas RQUICKI was similar between MAN and HIGHCR cows (P = 0.53). Within samples collected during the GTT, mean serum insulin concentrations and insulin:glucose ratio were greater (P < 0.01) in HIGH compared with HIGHCR cows, tended (P ≤ 0.09) to be greater in HIGH compared with MAN cows, and were similar (P ≥ 0.16) between HIGHCR and MAN cows. Serum glucose concentrations were greater (P < 0.01) for HIGH compared with MAN and HIGHCR cows 20 min relative to infusion. In conclusion, chromium propionate supplementation prevented the increase in insulin resistance caused by excessive energy intake in nonlactating dairy cows.

Thermoluminescence dating of Brazilian indigenous ceramics.

Two indigenous ceramics fragments, one from Lagoa Queimada (LQ) and another from Barra dos Negros (BN), both sites located on Bahia state (Brazil), were dated by thermoluminescence (TL) method. Each fragment was physically prepared and divided into two fractions, one was used for TL measurement and the other for annual dose determination. The TL fraction was chemically treated, divided in sub samples and irradiated with several doses. The plot extrapolation from TL intensities as function of radiation dose enabled the determination of the accumulated dose (D(ac)), 3.99 Gy and 1.88 Gy for LQ and BN, respectively. The annual dose was obtained through the uranium, thorium and potassium determination by ICP-MS. The annual doses (D(an)) obtained were 2.86 and 2.26 mGy/year. The estimated ages were approximately 1375 and 709 y for BN and LQ ceramics, respectively. The ages agreed with the archaeologists' estimation for the Aratu and Tupi tradition periods, respectively.

Chemical process to separate iron oxides particles in pottery sample for EPR dating.

Ancient potteries usually are made of the local clay material, which contains relatively high concentration of iron. The powdered samples are usually quite black, due to magnetite, and, although they can be used for thermoluminescene (TL) dating, it is easiest to obtain better TL reading when clearest natural or pre-treated sample is used. For electron paramagnetic resonance (EPR) measurements, the huge signal due to iron spin-spin interaction, promotes an intense interference overlapping any other signal in this range. Sample dating is obtained by dividing the radiation dose, determined by the concentration of paramagnetic species generated by irradiation, by the natural dose so as a consequence, EPR dating cannot be used, since iron signal do not depend on radiation dose. In some cases, the density separation method using hydrated solution of sodium polytungstate [Na6(H2W12O40).H2O] becomes useful. However, the sodium polytungstate is very expensive in Brazil; hence an alternative method for eliminating this interference is proposed. A chemical process to eliminate about 90% of magnetite was developed. A sample of powdered ancient pottery was treated in a mixture (3:1:1) of HCl, HNO(3) and H(2)O(2) for 4h. After that, it was washed several times in distilled water to remove all acid matrixes. The original black sample becomes somewhat clearer. The resulting material was analyzed by plasma mass spectrometry (ICP-MS), with the result that the iron content is reduced by a factor of about 9. In EPR measurements a non-treated natural ceramic sample shows a broad spin-spin interaction signal, the chemically treated sample presents a narrow signal in g=2.00 region, possibly due to a radical of (SiO(3))(3-), mixed with signal of remaining iron [M. Ikeya, New Applications of Electron Spin Resonance, World Scientific, Singapore, 1993, p. 285]. This signal increases in intensity under gamma-irradiation. However, still due to iron influence, the additive method yielded too old age-value. Since annealing at 300 degrees C, Toyoda and Ikeya [S. Toyoda, M. Ikeya, Geochem. J. 25 (1991) 427-445] states that E1'-signal with maximum intensity is obtained, while annealing at 400 degrees C E1'-signal is completely eliminated, the subtraction of the second one from 300 degrees C heat-treated sample isolate E1'-like signal. Since this is radiation dose-dependent, we show that now EPR dating becomes possible.

Shall we operate? Preoperative assessment in elderly cancer patients (PACE) can help. A SIOG surgical task force prospective study.

BACKGROUND: A number of elderly cancer patients do not receive standard surgery for solid tumors because they are considered unfit for treatment as a consequence of inaccurate estimation of the operative risk. To tailor treatment to onco-geriatric series, oncologists are now beginning to use a comprehensive geriatric assessment (CGA). This study investigates the value of an extended CGA in assessing the suitability of elderly patients for surgical intervention. PATIENTS AND METHODS: Preoperative assessment of cancer in the elderly (PACE) incorporates validated instruments including the CGA, an assessment of fatigue and performance status and an anaesthesiologist's evaluation of operative risk. An international prospective study was conducted using 460 consecutively recruited elderly cancer patients who received PACE prior to elective surgery. Mortality, post-operative complications (morbidity) and length of hospital stay were recorded up to 30 days after surgery. RESULTS: Poor health in relation to disability (assessed using the instrumental activities of daily living (IADL)), fatigue and performance status (PS) were associated with a 50% increase in the relative risk of post-operative complications. Multivariate analysis identified moderate/severe fatigue, a dependent IADL and an abnormal PS as the most important independent predictors of post-surgical complications. Disability assessed by activities of daily living (ADL), IADL and PS were associated with an extended hospital stay. CONCLUSION: PACE represents a valuable tool in enhancing the decision process concerning the candidacy of elderly cancer patients for surgical intervention and can reduce inappropriate age-related inequity in access to surgical intervention. It is recommended that PACE be used routinely in surgical practice.

Early detection of cancer: ideas for a debate.

Even if the overall number of cancer is increasing, the mortality has started to decrease in the Western World. The role of early detection in this decrease is a matter of debate. To assess its impact on mortality it is important to distinguish between diagnosis of cancer in symptomatic patients, and early detection in asymptomatic individuals who may self-refer or who may be offered ad hoc or systematic screening. The policies for early detection and screening vary greatly between European countries, despite many similarities in their cancer burden, and this partly reflects the uncertainties surrounding asymptomatic testing for cancer. A Task Force of European expert, held in Azzate (VA), Italy, established to address these issues, acknowledged the need for more research in the field of individual risk assessment since general statistics are more and more perceived as inadequate to design personal early detection plans. The group also recognised that combinations of early detection and screening will enforce the effectiveness of new treatments in curbing mortality curves, although policies will vary with different cancers.

Pre-operative assessment of cancer in the elderly (PACE): a comprehensive assessment of underlying characteristics of elderly cancer patients prior to elective surgery.

BACKGROUND: Cancer is a disease that particularly affects the elderly and, although surgery is the first treatment choice, many elderly cancer patients do not receive standard surgery because they are considered unfit for treatment due to an inaccurate estimation of operative risk. Pre-operative Assessment of Cancer in the Elderly (PACE) was developed in order to address the need to provide detailed information about the functional reserve of the elderly cancer patient to aid individualised management. METHODS: PACE incorporates a battery of validated instruments including the Comprehensive Geriatric Assessment (CGA), Brief Fatigue Inventory (BFI), Eastern Cooperative Oncology Group Performance Status (ECOG-PS), and American Society Anesthesiologists (ASA) grade. An international prospective study was conducted with 460 consecutive elderly cancer patients (216 breast, 146 GIT, 71 GUT, 27 other) receiving PACE prior to receiving elective surgery. RESULTS: Three hundred and eighty four patients (83.4%) were observed to have at least one co-morbidity; the most common being hypertension (n=246, 53.5%). More than two thirds of the patients had good functional and mental status according to PACE. After adjusting for age, sex and type of cancer, six of the seven items of PACE were found to be significantly associated with co-morbidities (according to the Satariano's Index of Co-morbidities (SIC)). A multivariate analysis identified IADL, BFI and ASA to be the most important instruments in explaining SIC. DISCUSSION: PACE has been effectively used to describe the functional capacity and health status in an international cohort of elderly cancer patients. The majority of PACE instruments have been found to be significantly associated with co-morbidities (SIC) and can distinguish between type and severity of cancer. PACE represents a useful tool in evaluating onco-geriatric fitness for surgery.

Evaluation of skin perfusion after nipple-sparing mastectomy by indocyanine green dye. Preliminary results.

The aim of the study was to investigate the blood supply of the normal nipple areola complex (NAC) and the spared areola complex after a nipple-sparing mastectomy using the analysis of the fluorescence from the indocianine green dye (ICG) injection. Between December 2002 and July 2003 we performed the ICG analysis in 10 cases of healthy breasts and in 9 patients after a nipple-sparing mastectomy and one patient after subcutaneous mastectomy. In all cases, the resulting fluorescence was measured in three different zones: nipple, areola, surrounding mammary skin. Three parameters of the fluorescence curve (slope, maximum intensity, time to achieve a maximum level) were recorded. On the healthy breast, the nipple showed a very high perfusion as compared to the other zones. On the contrary, after the mastectomy the fluorescent pattern was completely altered, being the perfusion of the nipple very low. In conclusion, these preliminary results confirm the applicability and the importance of the ICG technique for evaluating the perfusion of the healthy and spared areola after surgery. Because of the small number of patients further studies are needed.

Irradiation with standard tangential breast fields in patients treated with conservative surgery and sentinel node biopsy: using a three-dimensional tool to evaluate the first level coverage of the axillary nodes.

Recent data show that axillary coverage can be obtained, but only through a selective CT-based treatment planning, as standard tangential fields are inadequate to deliver therapeutic doses. Currently, the replacement of axillary dissection with new techniques, such as sentinel node (SN) biopsy, makes it necessary to re-address the question about the real role of axillary irradiation, complicated by the differences in the anatomy of dissected and undissected axillary regions. The purpose of this paper is the dosimetric analysis of first axillary level coverage in standard irradiation of 15 breast-cancer patients treated with quadrantectomy and SN biopsy (negative finding). During surgery a clip on the site of the SN was positioned, marking the caudal margin of first axillary level. After the breast treatment plan was completed, the first axillary level was contoured on CT scans, from the site of the surgical clip up to the sternal manubrium, for coverage analysis with dose-volume histograms (DVHs) and three-dimensional isodose visualization. The maximum dose mean ranged from 5% to 80% of the prescribed dose (mean value 48.7%). The mean total dose received by the volume of interest was lower than 40 Gy in all but one patient. No patient had total irradiation of first nodal level; only one patient had 35% of the volume enclosed in the 100% isodose. Our analysis lead to the conclusion that therapeutic doses are not really delivered to first level axillary level nodes by a standard tangential field technique, and that specific treatment planning and beam arrangement are required when adequate coverage is necessary.

Surgical technique of mammosite RTS implant for accelerated radiation delivery in breast conserving surgery.

Breast conserving surgery followed by radiation therapy has been accepted as an alternative to mastectomy in the management of patients with early-stage breast cancer. Over the past decade there has been increasing interest in a variety of radiation techniques designed to treat only the portion of the breast deemed to be at high risk for local recurrence and to shorten the duration of treatment. This article describes the surgical technique of implant of a new device developed with the goal of making breast conserving therapy more widely adopted. Our preliminary results showed that breast conserving therapy, using high dose-rate brachytherapy delivered with this new device as the sole radiation modality, is both technically feasible and well tolerated by the patients with excellent cosmetic results. This new method seems to be an important step forward in the search for a more conservative treatment for women with breast cancer, and for providing a better quality of life.

A prospective, randomized, controlled clinical trial of tissue adhesive (2-octylcyanoacrylate) versus standard wound closure in breast surgery.

BACKGROUND: Recent studies suggest that the use of tissue adhesive for closure of both traumatic lacerations and incisional surgical wounds leads to cosmetic outcome comparable to conventional sutures. To date, no studies have investigated tissue adhesive in breast surgery and costs. Our aim was to compare the tissue adhesive 2-octylcyanoacrylate (OCA) with standard suture in breast surgery. METHODS: A prospective randomized study was conducted in which 151 patients were assessed for eligibility, and 133 were randomly allocated to skin closure with OCA adhesive or monofilament suture. Cosmetic outcome with blinded assessment, wound management by the patients, complication rates, and economic outcome were recorded. RESULTS: There was no difference in cosmetic score in the 2 groups, nor in complications at the early, 6-month, and 1-year follow-up. Patient satisfaction with the wound closed with OCA was rated significantly higher when compared with standard suture (P <.0001). The application of the tissue adhesive was significantly faster than that for standard suture (P <.001). In economic terms total costs were less in the tissue adhesive group, mainly due to lower postoperative costs of physician and assistant services (P <.001). CONCLUSIONS: OCA is effective and reliable in skin closure for breast surgery, yielding similar cosmetic results to standard suture. OCA is faster than standard wound closure and offers several practical advantages over suture repair for patients. Cost analysis has found that OCA adhesive can significantly decrease health care costs.

Complete nodal staging in male breast cancer. (Biopsy of axillary and internal mammary sentinel node).

Carcinoma of the male breast is an uncommon phenomenon, accounting for < 1% of all malignancies in men. Searching for a more conservative treatment we introduced in our clinical practice axillary sentinel node biopsy and, if present, sentinel node biopsy of the internal mammary chain. The potential clinical implications of complete nodal staging are far-reaching, and give us a major new opportunity to stratify male patients with breast cancer for appropriate surgery as well as giving valuable prognostic information.

The surgical management of elderly cancer patients; recommendations of the SIOG surgical task force.

Although cancer in the elderly is extremely common, few health professionals in oncology are familiar with caring for series of oncogeriatric patients. Surgery is at present the first choice, but is frequently delivered suboptimally: under-treatment is justified by concerns about unsustainable toxicity, whilst over-treatment is explained by the lack of knowledge in optimising preoperative risk assessment. This article summarises the point of view of the Surgical Task Force @ SIOG (International Society for Geriatric Oncology), pointing out differences from, and similarities to, the younger cohorts of cancer patients, and highlighting the latest updates and trends specifically related to senior cancer patients.

Recognizing features that are dissimilar in male and female breast cancer: expression of p21Waf1 and p27Kip1 using an immunohistochemical assay.

BACKGROUND: Male breast cancer (MBC) is an uncommon disease, and most of our current knowledge of its biology, natural history and treatment has been extrapolated from data on the disease in women. Information is still needed on the molecular biological properties of male breast tumors and their predictive relevance. Kinase inhibitor proteins (KIPs) p27Kip1 and p21Waf1 negatively regulate cell cycle progression by preventing the passage of cycling cells from G1 to S phase through G1 cyclin-dependent kinase activation. No studies exist on the role of these factors in male breast carcinoma. PATIENTS AND METHODS: We have retrospectively analyzed the immunohistochemical expression of p21Waf1 and p27Kip1 protein in 27 primary MBC and in 101 female breast cancers (FBC) treated at the European Institute of Oncology between 1997 and 2000. We also assessed sex hormone receptors status, p53, bcl-2 and c-erb-B2 protein expression, and Ki-67 labeling index. RESULTS: We observed a statistically significant difference in the immunostaining of KIPs p27Kip1 and p21Waf1 in male patients compared with females. Expression of p21Waf1 was observed in 19 of the 27 (70.3%) primary MBCs versus 29 of 101 FBC (29%). Fourteen of 22 negative c-erbB-2 MBCs cases expressed immunostaining for p21Waf1 (P = 0.05). p27Kip1 immunoreactivity was been detected in 26 of 27 (96.2%) male breast patients versus 39 of 101 FBC (39.3%) (P = 0.000). Highly positive staining for P27Kip1 was found in 21 of 25 androgen receptor-expressing samples. Higher levels of p27Kip1 were expressed in bcl-2-positive samples (17 of 20). Eighteen of 22 c-erbB-2-negative cases were strongly immunoreactive for p27Kip1. CONCLUSIONS: p27Kip1 and p21Waf1 immunoreactivity is higher in MBCs compared with FBCs. The findings of higher p27Kip1 and p21Waf1 immunostaining may be an additional predictive factor in MBC. These biological features could be possible indicators for different biological pathways in the tumorigenesis of MBCs.