Premalignant diseases of the breast

The importance of identifying women at increased risk for developing breast cancer is obvious. Environmental and host factors as well as breast histology are reviewed in this article.     

Premalignant tumors and conditions of bone.

Most bone sarcomas arise in apparently normal bone. However, some sarcomas arise in preexisting benign bone tumors or in nonneoplastic conditions. Some of the lesions, such as multiple exostoses and Ollier's disease, have a propensity to develop chondrosarcoma. Rarely does a benign giant cell tumor become malignant without prior irradiation, malignant transformation of other benign tumors, such as osteoblastoma and chondroblastoma, is a medical curiosity. Among nonneoplastic conditions, radiation changes, long-standing chronic osteomyelitis, and Paget's disease have definite premalignant connotations. However, the risk of developing cancer in these conditions is still low.     

Unilateral male breast masses: cancer risk and their evaluation and management

Breast cancer is an uncommon cause of breast enlargement in the adult male. Overall, it accounts for <1 per cent of all male cancers. Although most male breast carcinomas are clinically apparent, distinguishing early breast cancer from gynecomastia, the most common cause of male breast enlargement, is considered a difficult task. To overcome this difficulty, many surgeons proceed directly to surgery as their initial diagnostic test. Although appropriate in some cases, the infrequent occurrence of male breast cancer and the diagnostic accuracy of mammography and fine-needle aspiration cytology suggest a modification of our present management. The aim of this study was to assess the incidence of breast cancer in men with unilateral breast masses and to propose a treatment algorithm for unilateral male breast masses. The medical records of 36 male patients who underwent subcutaneous mastectomy for a unilateral breast mass at the Buffalo Veterans Administration Medical Center between 1989 and 1996 were retrospectively reviewed. Data was collected on a standard data form. The median age was 63-years-old (range, 22-82). Gynecomastia was diagnosed in 30 patients (83%), lipoma in 4 patients (11%), invasive breast cancer in 1 patient (3%), and melanoma in situ in 1 patient (3%). Of the 30 patients with gynecomastia, 60% (18 patients) gave a history of a medical condition or use of medications known to cause gynecomastia, compared with 16 per cent (1 of 6) of the patients without gynecomastia (P = 0.08). Half of the patients with gynecomastia presented with an asymptomatic mass compared with 67 per cent of the patients without gynecomastia (P = not significant). The median duration of symptoms for patients with gynecomastia was 3 months. Men with unilateral breast masses have a low incidence of breast cancer. A male patient with a palpable unilateral breast mass consistent with gynecomastia on the basis of historical, physical and mammographic findings does not require surgical biopsy unless other clinical indications prevail. Lack of symptoms (pain) related to the mass is probably not helpful in deciphering gynecomastia from breast cancer.     

Immunologically measured serum markers and their role in the management of prostate cancer

Serum prostatic acid phosphatase and prostate-specific antigen have been measured in a group of 106 cases of newly diagnosed prostate cancer. The serum levels of the tumour markers have been correlated with the clinical and ultrasound staging of the prostate cancer at diagnosis. All patients were managed by a deferred treatment policy. Patients without detectable metastases at presentation have been assessed after a period of 2 years to determine if the level of serum tumour markers at diagnosis could predict subsequent disease progression. The study has demonstrated that a combination of immunologically measured acid phosphatase and prostate-specific antigen is the best method of assessing the prognosis of an individual prostate cancer at the time of presentation.     

Evaluation and management of high risk and premalignant lesions of the breast

Specific, combined histologic and cytologic patterns of atypical epithelial hyperplasia (AH) in the breast indicate a medically relevant risk of breast cancer development in 5% to 10% of women with otherwise benign biopsies. This risk is four to five times that of similar women without such lesions, that is, women of the same age and at risk for the same period of time. These relative risks are not stable and fall 10 to 15 years after detection, more closely approximating the risks of women of comparable age. Proliferative disease without atypia, no matter how extensive or complex, predicts only a slight elevation of risk, which approaches double that of the reference population. There is a strong interaction of AH with family history of breast cancer in at least a first degree relative. This risk doubles the risk of AH alone and is approximately 20% at 10 to 15 years after biopsy, particularly for women in their forties and early fifties. These considerations are of less clinical importance in women over age 60. Low replacement doses of conjugated estrogen after the menopause do not further elevate risk beyond that identified by histologic patterns. Noncomedo ductal carcinoma in situ may be considered a true precursor lesions; however, it differs significantly in many ways from the more advanced lesion recognized as the comedo type of ductal carcinoma in situ. Small examples of noncomedo ductal carcinoma in situ can eventuate in invasive carcinoma after 6 to 10 years. They may be treated by wide local excision without radiation, with no recurrence up to 8 to 10 years in all likelihood. Ductal carcinoma in situ lesions can be extensive within the breast, and this conservative posture should be reserved for smaller lesions.

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Resumen Patrones histológicos y citológicos combinados de hiperplasia epitelial atípica (HA) en la glándula mamaria son indicativos de un riesgo de desarrollar cáncer del orden de 5 a 10% en las mujeres con lesiones por lo demás benignas. El riesgo es 4–5 veces mayor que el de mujeres de poblaciones similares que no poseen tales lesiones. Tales riesgos relativos no son estables, y disminuyen 10–15 años luego de la detección, para aproximarse a los riesgos de mujeres de edades comparables. La enfermedad proliferativa sin atipia, no importa qué tan extensa o compleja sea, predice un ligero riesgo mayor, el cual se acerca al doble del de la población de referencia.Hay una fuerte interacción de la HA con la historia familiar de cáncer mamario en por lo menos los familiaries de primer grado. Tal riesgo dobla al riesgo de HA sola, la dobla y se aproxima al 20% a los 10–15 años después de la biopsia, en particular en mujeres en las edades de los 40 y los primero 50 años, pero tales consideraciones son de menor importancia clínica en mujeres de 60 años. Los estrógenos conjugados en dosis bajas, administrados después de la menopausia, no parecieron incrementar el riesgo por encima del que fue identificado mediante patrones histológicos.Sólo el carcinoma in situ de tipo no comedo puede ser considerado como lesión precursora pero que no da lugar al tratamiento más extenso que se recomienda para el tipo más avanzado de comedo carcinoma ductal in situ. Pequeños carcinomas ductales in situ de tipo no comedo pueden resultar en carcinoma invasivo en un periodo de 6 a 10 años. Estos pueden ser tratados con resección local amplia sìn ìrradiación, pudiendose esperar que probablemente no se presentara recurrencia hasta en 8–10 años de seguimiento. Los carcinomas ductales in situ pueden ser lesiones muy extensas, y esta conducta conservadora debe ser reservada para las lesiones menores.

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Résumé Il existe chez 5 à 10 % des femmes qui ont apparemment des résultats normaux de biopsies mammaires, des aspects histologiques et cytologiques d'hyperplasie épithéliale atypique (HEA) du sein qui semblent prédire un certain risque de développer un cancer du sein. Ce risque a été estimé à 4–5 fois celui que présentent les femmes du même âge avec les mêmes autres facteurs de risque, mais qui n'ont pas de telles anomalies histo-cytologiques. Ce risque n'est cependant pas constant et semble diminuer avec le temps, rejoignant le même risques qu'ont d'autres femmes aux mêmes âges 10 à 15 ans après la première détection de ces anomalies. Le risque de voir se développer une prolifération sans atypie cellulaire, même extensive ou complexe, n'est que deux fois celui de la population en générale. L'HEA se voit souvent dans la fratrie des familles a cancer du sein, du moins chez les cousines au premier degré. Ce risque, deux fois celui de l'HEA, se situe à 20% environ 10–15 ans après la biopsie, en particulier chez les femmes de la cinquième (40–49) ou au début de la sixième (50) décennie. Ces considérations ont moins d'importance après l'âge de 60 ans. Un traitement par des oestrogènes à de faibles doses après la ménopause ne semble pas augmenter ce risque. Seuls les cancers intracanalaires in situ non comédocarcinomateux peuvent être considérés comme des lésions précancéreuses et ne nécessitent pas de traitement étendu, que nécessitent, par contre, les lésions du type comédocarcinome, même in situ. Des lésions non comédocarcinomateuses peuvent parfois devenir des cancers invasifs en 6 à 10 ans. Il faut les

     

Surgical management of the patient at high risk for breast cancer

The most controversial aspect of breast disease centres around the management of patients who have either a strong family history of breast cancer or a biopsy diagnosis of lobular carcinoma in situ or ductal carcinoma in situ. The current alternatives for patients who have two or more relatives with breast cancer consist of close follow-up or prophylactic total mastectomies and reconstruction. Invasive breast cancer in patients with lobular carcinoma in situ may occur in either breast and may be as high as 30% at 20 to 30 years. In these women it is reasonable to do a wide excision of the lobular carcinoma; in those without a family history, close follow-up is adequate. Intraductal cancer treated by biopsy only is associated with a 40% risk of cancer in the ipsilateral breast. Therefore, the usual management is total mastectomy. However, the information to support this therapy over a segmental resection has limited scientific validity. Because the cosmetic appearance after total mastectomy and reconstruction is not as good as that of the normal breast, this procedure must be employed cautiously and only with the total support of the patient and her husband or close family. Subcutaneous mastectomy for prophylaxis leaves behind macroscopic glandular tissue and, therefore, is not considered by many to be optimal management. A total mastectomy, preserving the skin and resecting all macroscopic breast tissue and nipple, is the treatment of choice if the procedure is deemed appropriate.     

Supracondylar humerus fractures in children: the effect of weather conditions on their risk

Introduction

Supracondylar humerus fractures are the most common fractures of the elbow in children. Many environmental factors such as weather conditions may affect the risk of these fractures. The purpose of the study was to analyze the effect of weather conditions (temperature, rainfall, wind) on fracture risk in children <16 years of age during the extended summer time period with the absence of snow cover.

Materials and methods

All children <16 years of age with an outdoor supracondylar humerus fracture between May 1 and September 30 in a defined geographical area during the decade of 2000–2009 were included. Daily meteorological recordings for altogether 1526 study days were reviewed from the national weather service and the association of weather conditions and fractures were analyzed.

Results

A majority (79.7%, N = 181) of the fractures occurred on dry days versus rainy days (20.3%) (P = 0.011), and risk of a fracture was 3.5-fold higher on dry days as compared with rainy days (crude OR 3.5, 3.41–3.59, P < 0.001). The weather was warm, instead of cool or hot, when the majority of the fractures (N = 147, 64.8%) occurred (P = 0.008): Warm temperatures (15–24.9 °C) increased the fracture risk 2.6-fold (crude OR 2.64, 2.59–2.70, P < 0.001), compared with cool (<15 °C) days. The fracture incidence did not change according to the wind speed (P = 0.171). The findings were similar through the school term and summer vacation.

Conclusion

Dry and warm weather conditions increase the risk of outdoor supracondylar humerus fractures in children during the time period with the absence of snow cover.

     

Confidence of graduating family practice residents in their management of musculoskeletal conditions

A study was undertaken to determine the confidence of graduating family practice residents in the management of musculoskeletal conditions and to determine the level of exposure of graduating family practice residents to fracture care. A 2-page questionnaire consisting of 50 items was sent to 680 graduating family practice residents at 100 randomly selected residency training programs throughout the United States. Family practice residents were questioned about their fracture care experience, including the number of fractures diagnosed, the number of fractures reduced, the number of fractures treated to healing, and the number of casts and splints applied. Residents were also asked about their training experience on an orthopedic surgery service. Residents were asked to rate their confidence on a scale of 1 (least confident) to 10 (most confident) in the physical examination, radiographic evaluation, diagnosis, and treatment of a variety of musculoskeletal conditions, including physical examination of the knee, lower back, ankle, wrist, cervical spine, shoulder, hand, and foot; radiographic evaluation of the lumbosacral spine, traumatic cervical spine, hand injuries, adult shoulder trauma, osteomyelitis, and pediatric elbow injuries; diagnosis of carpal tunnel syndrome, herniated lumbar disc, knee instability, rotator cuff tear, and shoulder instability; and treatment of ankle sprain, tennis elbow, olecranon bursitis, distal radius fracture (Colles), bimalleolar ankle fracture, hip avascular necrosis, knee dislocation, and pediatric elbow fracture. These results were compared with graduating family practice residents' confidence in the physical examination, radiographic evaluation, diagnosis, and treatment of a variety of nonmusculoskeletal conditions. Completed questionnaires were returned by 351 graduating family practice residents. The overall fracture care experience of graduating family practice residents was minimal. Seventy-nine percent of graduating residents had reduced 5 or fewer fractures during their entire residency training program. Experience with cast and splint application was also relatively limited. Graduating family practice residents reported an average of 5.1 weeks (range, 0-10 wk) of training experience on an orthopedic surgery service during their residency. Graduating family practice residents were significantly more confident in the physical examination, radiographic evaluation, diagnosis, and treatment of nonmusculoskeletal conditions than in those of musculoskeletal conditions (P = .0001). Family practice residents who had rotated on an orthopedic service for 8 weeks or more during their training reported significantly higher confidence for all 4 skills-physical examination (P = .003), radiographic evaluation (P = .003), diagnosis (P = .007), and treatment (P = .009). In conclusion, family practice residents show relatively low confidence in the management of musculoskeletal conditions and receive minimal exposure to all aspects of fracture care. Confidence can be improved with greater exposure to the musculoskeletal sciences--such as a rotation of 8 weeks or more on an orthopedic surgery service.     

Volatile markers of breast cancer in the breath

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.     

Endocrine markers in argyrophilic carcinomas of the breast

Argyrophilia in breast carcinomas is of uncertain significance. We tested a series of 20 cases of Grimelius-positive carcinomas with immunocytochemical markers of endocrine or exocrine differentiation. Fifty per cent of these tumors were positive, in a variable percentage of the neoplastic cells, with monoclonal antibodies against chromogranin, a specific marker of neuroendocrine differentiation. All cases were positive for neuron-specific enolase, but the significance and specificity of the reaction remain doubtful. The apparent positivity for alpha-lactalbumin, as found also by Clayton and coworkers, was found to be related to a contaminant, which is in fact also an endocrine marker. As with other types of breast carcinoma, all our cases were positive for epithelial membrane antigen, evidence that argyrophilic breast carcinomas, and specifically the chromogranin-positive subgroup, should be interpreted as endocrine neoplasms displaying multidirectional differentiation.     

Breastfeeding and prognostic markers in breast cancer

Background

Several studies suggest that total breastfeeding time reduces breast cancer risk. The underlying mechanisms are unclear. Whether breastfeeding also affects the prognosis is not yet investigated. A number of tumour characteristics, i.e. histological type of cancer, grade, tumour size, Nottingham prognostic index, vascular invasion and DNA-ploidy, have been demonstrated to be of prognostic value.

Methods

We have searched for a possible link between these prognostic markers and breastfeeding time, age at first child and number of children. 250 women treated for breast cancer have answered a questionnaire.

Results

No significant interactions were found possibly with one exception, LVI vs. age at first child. We found, significant correlations between lobular cancer, and thereby also DNA-ploidy, and age at first childbirth.

Conclusions

We have found that lobular cancer (and thereby also diploid tumours) are connected, independently, to age at first childbirth and possibly also to number of children but no other correlations between reproductive data, breastfeeding included, and prognostic markers used in this study were found.     

Tumor markers in breast and endometrial cancer

Basic studies developed from human cell lines or tissue biopsies have allowed to isolate monoclonal antibodies and complementary DNAs specific for tumoral antigens and rare proteins implicated in the control of cancer growth and invasiveness. Present clinical studies indicate that some molecular probes display a potential value as markers of tissue specificity, of hormone dependency or prognosis in breast and endometrial cancers.