Role of sentinel lymph node biopsy in early breast cancer.

Current literature has suggested that sentinel lymph node biopsy may replace axillary dissection as the nodal staging procedure of choice in early breast cancer. The aim of this study is to evaluate the effectiveness and accuracy of sentinel lymph node biopsy using methylene blue dye in predicting axillary nodal status in early breast cancer with clinically impalpable axillary lymph nodes. In the period between June 2005 and May 2009, 50 patients with early breast cancer and clinically impalpable axillary lymph nodes, underwent sentinel lymph node biopsy using methylene blue dye followed by completion of axillary dissection in the same setting after taking a written consent from the patients. Of the included 50 patients, sentinel lymph node biopsy was successful in 48 patients (96.0%). Accuracy of sentinel lymph node biopsy was 95.8%, sensitivity was 90.0%, false negative rate was 6.7%, negative predictive value was 93.3%.

Pathology of invasive breast disease.

Invasive breast cancers constitute a heterogeneous group of lesions. Although the most common types are ductal and lobular, this distinction is not meant to indicate the site of origin within the mammary ductal system. The main purpose of the identification of specific types of invasive breast carcinoma is to refine the prediction of likely behavior and response to treatment also offered by the other major prognostic factors, including lymph node stage, histologic grade, tumor size, and lymphovascular invasion.

Cáncer de mama en mujeres de edad media evaluación de los factores de riesgo / Breast cancer in medical age woman risk factors evaluation

Evaluar factores de riesgo para cáncer de mama en pacientes de edad media en comparación con riesgo de mujeres jóvenes y tercera edad, estudiar si la mayor frecuencia de cáncer de mama en edades medias está en relación con la distribución de la población venezolana. En 515 pacientes 36 (7 por ciento) menores de 40 años, 379 (74 por ciento) entre 40 y 64 años, y 100 (19 por ciento) mayores de 64 años. Se analizaron antecedentes familiares de cáncer de mama, ovario, factores de riesgo hormonales (endógenos y exógenos) antecedentes de patología mamaria benigna. Se calcularon tasas por 100.000 habitantes. El grupo de edad media se asemeja al de la tercera edad con referencia a antecedentes familiares de cáncer de mama y ovario; y al grupo de pacientes jóvenes con referencia al promedio del número de abortos, nuliparidad e ingestión de anticonceptivos orales. Los tres grupos son diferentes con respecto al promedio del número de embarazos a término y son similares en cuanto a la menarquía, el promedio de edad del primer embarazo a término, la lactancia y antecedentes de patología mamaria benigna. Hubo tasas similares en el grupo de edad media y de la tercera edad. El cáncer de mama en mujeres de edad media tiene factores de riesgo similares al de mujeres jóvenes y tercera edad, observamos que la mayor frecuencia de cáncer en edad media puede atribuirse a distribución general de la población venezolana

The objective of this study is to known risk factors for breast cancer in the middle age patients in comparison with the younger and the older patients. In addition, we must study whether the high frequency of middle age patients is attributable to venezuelan population distribution. Only five hundred fifteen patients with breast cancer were included in our study; 36 (7 percent) younger than 40 years old, 379 (74 percent) between 40 and 64 years old, and 100 (19 percent) older than 64 years old. We analyzed the family history of the breast and the ovarian cancer, and the hormonal risk factors (The endogenous and the exogenous), and previous benign breast disease. In addition, we measured teases for 100 000 habitants. The middle age group was similar to the older group according to the family history of breast and the ovarian cancer; and similar to the younger group according to number of abortions, null parity, and oral contraceptives ingestion. The three groups were different according to number of terminal pregnancies and similar according to menarche, mean age of first terminal pregnancy, lactation, and previous benign breast disease. There were similar teases in the middle age and older patient groups. The middle age group has similar risk factors for breast cancer shared between older and younger groups; besides, the high frequency of breast cancer in the middle age group can be attributable to the venezuelan population distribution

The adjacent vessel sign on breast MRI: new data and a subgroup analysis for 1,084 histologically verified cases.

OBJECTIVE: The adjacent vessel sign (AVS) is a descriptor for differentiating malignant from benign breast lesions on breast MRI (bMRI). This investigation was designed to verify the previous reports on the diagnostic accuracy of AVS and to assess correlation between AVS, histopathological diagnosis, lesion size and lesion grade. MATERIALS AND METHODS: This study was approved by the local ethical committee. Experienced radiologists evaluated 1,084 lesions. The exclusion criteria were no histological verification after bMRI and breast interventions that were done up to one year before bMRI (surgery, core biopsy, chemo- or radiation therapy). The native and dynamic contrast-enhanced T1-weighted series were acquired using standardized protocols. The AVS was rated positive if a vessel leading to a lesion could be visualized. Prevalence of an AVS was correlated with the lesions' size, grade and histology using Chi-square-tests. RESULTS: The AVS was significantly associated with malignancy (p < 0.001; sensitivity: 47%, specificity: 88%, positive-predictive-value [PPV]: 85%). Malignant lesions > 2 cm more often presented with an AVS than did those malignant lesions < 2 cm (p < 0.0001; sensitivity: 65%, PPV: 90%). There was no correlation of the AVS with the tumor grade. The prevalence of an AVS didn't significantly differ between invasive lobular carcinomas versus ductal carcinomas. In situ cancers were less frequently associated with an AVS (p < 0.001). CONCLUSION: The adjacent vessel sign was significantly associated with malignancy. Thus, it can be used to accurately assess breast lesions on bMRI. In this study, the AVS was particularly associated with advanced and invasive carcinomas.

Decreasing trend of tumor size and downstaging in breast cancer in Iran: results of a 15-year study.

The aim of this cross-sectional study was to show the characteristics of breast cancer across a period of 15 years according to pathological records in Tehran, Iran. In the year 1985, a 20-year study was designed and developed in five major hospitals in Tehran to study the burden and characteristics of breast cancer in Iran. This study is based on the data collected from 1986 through 2000. SPSS version 13 was used for statistical analysis. In this study, 1612 female breast cancer records were reviewed. The mean age of patients was 47.95+/-12.42 years with a median of 47 years. Over the study period, the proportion of tumors diagnosed at T2 increased with a decline in the proportion of T3 cases. Similarly, the percentage of stage II cases at diagnosis increased, whereas stage III decreased. We detected a decrease in tumor size and downstaging of female breast cancer in Tehran, Iran. This can be attributed to the overall improvement in the level of health in Iran and also educational activities that teach women how to perform breast self-exam and when and why to ask for breast examination.

Risk-benefit analysis of preoperative breast MRI in patients with primary breast cancer.

AIM: To analyse and compare the risks and benefits of preoperative breast MRI (BMRI) in patients with primary breast cancer (PBC), and to determine the influence of mammographic breast density (BD) and histological tumour type (TT). MATERIALS AND METHODS: One hundred and nineteen patients who underwent preoperative bilateral breast MRI for staging of PBC during a 1-year period from July 2005 to August 2006 were prospectively evaluated. Changes in clinical management due to BMRI findings were recorded. MRI-detected lesions were correlated with histology. Additional MRI-detected malignant lesions and spared additional biopsies because of negative MRI in case of unclear ultrasound findings were determined as beneficial for the patient. Biopsies of benign MRI detected lesions were defined as disadvantageous. The influence of BD (ACR 1-4) and TT on the change in clinical management and patient benefit was evaluated. RESULTS: The findings of the BMRI examinations changed the clinical management in 48 patients (40.3%). Seventeen women underwent mastectomy instead of breast conservation, eight patients underwent extended excision, 21 additional lesions were clarified by MRI intervention, and two ultrasound-detected lesions were not biopsied because of negative MRI. Histologically malignant additional or extended biopsies (n=34) and two cases of spared biopsies resulted in 36 (30.3%) women who benefited from preoperative BMRI. Twelve patients (10.1%) had additional biopsies of MRI-detected benign lesions, and therefore, had an unfavourable outcome due to BMRI. The change in clinical management and patient benefit were independent of BD and TT (p>0.05). CONCLUSION: Preoperative BMRI was beneficial for 30.3% of 119 patients with PBC. The percentage of additional biopsies of benign lesions (10.1%) seems acceptable.

Estudio inmunohistoquímico del carcinoma de glándula mamaria: en el Hospital Vargas de Caracas / Immunohistochemical study of mammary gland carcinoma: in Hospital Vargas de Caracas

Estudiar la asociación entre diferentes elementos morfológicos con aspectos inmunohistoquímicos y su posible utilidad pronóstica. Estudio descriptivo-retrospectivo, de 651 casos de carcinoma mamario con marcaje inmunohistoquímico en el Hospital Vargas de Caracas desde mayo 2001 a julio 2004. Se analizaron características morfológicas de los diferentes tipos tumorales, aplicando la clasificación de Scarff-Bloom-Richardson modificada, relacionándolos con la expresión de diferentes marcadores inmunohistoquímicos: receptores de estrógeno, receptores de progesterona, c-erbB-2 y Ki-67, realizados mediante la técnica de biotina-estreptavidina. La edad promedio fue 51,72 años. El tumor más frecuente fue el carcinoma ductal infiltrante (88,7 por ciento), seguido del carcinoma lobulillar infiltrante (4,6 por ciento). El 5,5 por ciento de los carcinomas ductales eran bien diferenciados, 42,3 por ciento moderadamente diferenciados, 52,2 por ciento poco diferenciados; de estos, el 77 por ciento tenían receptores de estrógeno y de progesterona ≤ 10 por ciento; los carcinomas bien diferenciados mostraron positividad variable. Los tumores poco diferenciados presentaron c-erbB-2 positivo en 51,36 por ciento, entre los bien diferenciados el 81,84 por ciento fueron negativos, el carcinoma intraductal fue positivo en un 42,86 por ciento, generalmente asociado a comedocarcinoma. El 94,37 por ciento de los tumores poco diferenciados fueron Ki-67 positivos. El carcinoma ductal infiltrante de tipo clásico es el tumor maligno más frecuente de la glándula mamaria, con una edad promedio de 51,5 años, generalmente es poco diferenciado, implicando posiblemente tumores con conducta biológica agresiva. Esto se evidencia por la negatividad para receptores hormonales y la expresión aumentada de c-erbB-2 y Ki-67.

To study and assess the association between different morfhological and pathologic features and immunohistochemistry as a prognostic factor. A retrospective-descriptive study of 651 cases of breast cancer by immunohistochemistry markers was analyzed in the Vargas Hospital of Caracas since may 2001 until july 2004. We evaluate the pathologic features of the different tumor subtypes, and relation this with the expression of immunohistochemistry markers: the estrogen receptor, progesterone receptor, c-erbB-2 and Ki-67, made by the biotin-streptavidin technique. The median patient age was 51.72 years. The most frequent type of tumor was the invasive duct carcinoma (88.7 %), follow by the invasive lobular carcinoma (4.6 %). The 5.5 % of the duct carcinomas were well differentiated tumors, 42.3 % moderate differentiated, and 52.2 % poorly differentiated; in which 77 % had estrogen receptor and progesterone receptor ≤ 10 %, well differentiated tumors show a variable positivity. The poorly differentiated tumors show positive c-erbB-2 in 51.36 %, in the well-differentiated group 81.84 % were negative; the c-erbB-2 on intraductal carcinoma was positive in 42.86 %, generally associated with the comedocarcinoma; the 94.7 % of the poorly differentiated tumors were Ki-67 positives. Classic invasive duct carcinoma is the most frequent malignant tumor, with a median age of 51.5 years, and the poorly differentiated tumors generally show an aggressive biologic conduct, associated to patients with estrogen receptors and progesterone receptors negative tumors and a high expression of the c-erbB-2 y Ki-67.

Central quadrantectomy with resection of the nipple-areola complex compared with mastectomy in patients with retroareolar breast cancer.

Appropriate surgery in women with retroareolar breast cancer should allow resection of the cancer with wide free margins and an acceptable cosmetic result. The aim of this study was to compare breast conservation surgery (BCS) to mastectomy for treatment of retroareolar breast cancer. In a prospective nonrandomized study, 69 women with retroareolar breast cancers underwent either central quadrantectomy (n=33) with complete removal of the nipple-areola complex or mastectomy (n=36). Two of 33 (6%) patients scheduled for BCS had a secondary mastectomy and immediate reconstruction due to involved margins. After a median follow-up of 42 month (range 17-99 months) in the BCS group and 43 months (range 16-118 months) in the mastectomy group local and regional recurrences as well as systemic disease were comparable between both groups. The postoperative cosmetic result after BCS as evaluated by the patients was rated as excellent in 80% and good in 20% with no poor result. BCS followed by radiation therapy is a feasible alternative to mastectomy in patients with retroareolar breast cancer.

Significance of pathological evaluation for lymphatic vessel invasion in invasive breast cancer.

BACKGROUND: Lymphatic vessel invasion (LVI) has been conventionally assessed on hematoxylin-eosin (HE) stained sections, but this assessment tends to be subjective. The aim of this study is to investigate the significance of LVI in invasive breast cancers, primarily using immunohistochemical lymphatic endothelial markers. METHODS: We studied 69 invasive breast carcinoma cases. Using D2-40 and podoplanin, we investigated the distribution of lymphatic vessels around the tumor and LVI, and they were compared with the HE sections. The correlation between LVI, lymph node metastasis and disease free survival (DFS) was also investigated. RESULTS: Lymphatic vessels were most frequently seen outside the tumor (86%), whereas lymphatic vessels were not seen in the central zone of the tumor. LVI was found in 22 cases, of which nineteen was seen in the peripheral zone (87%). For both HE and lymphatic markers, the rates of mild LVI tended to be high. The concordance rate between D2-40 and podoplanin was 94.2% (65/69). LVI assessed on HE sections was corresponded to 54/69 cases (78.2%) using either D2-40 or podoplanin. There were 25 axillary lymph node positive cases. Lymph node metastasis significantly correlated with LVI assessed by HE section, but did not correlate with LVI assessed by the lymphatic markers. The tumor recurred in 19 cases during the mean follow-up period of 47.5 months. Disease free survival was significantly better for LVI negative cases on HE analysis, and LVI negative or mildly positive by any staining procedure. CONCLUSION: The lymphatic endothelium markers, D2-40 and podoplanin, are very useful for detecting LVI, but careful examination by routine HE sections may be enough for routine practice. Moderate or marked degree of LVI may be of value to predict survival.

COX-2 expression in lobular in situ neoplasia of the breast: correlation with histopathological grading system according to the Tavassoli classification.

AIMS: There is considerable evidence to link cyclooxygenase (COX)-2 to the development of cancer. The aim of this study was to assess COX-2 expression and its subcellular localization in lobular in situ neoplasia (LIN) of the breast and to verify differences in COX-2 expression between different grades of lesions according to the Tavassoli classification. METHODS AND RESULTS: We analysed the expression of COX-2 protein by immunohistochemistry in tissue samples of 51 LIN lesions classified into three grades according to the Tavassoli classification. COX-2 immunostaining was observed in 78.4% of LIN samples and showed a prevalent membranous rather than cytoplasmic pattern. COX-2 was expressed in 16/17 (94.1%) LIN1, 22/25 (88%) LIN2 and 2/9 (22.2%) LIN3. As regards COX-2 expression, a statistically significant difference was found between LIN1 and LIN3 (P = 0.001) and between LIN2 and LIN3 (P =0.001). No difference was found between LIN1 and LIN2. Moreover, a significant negative correlation was found between LIN grade and COX-2 expression (P < 0.0001). CONCLUSIONS: COX-2 is highly expressed in LIN, supporting a role for this protein in the early stage of breast carcinogenesis, representing the rationale for using COX-2 selective inhibitors in the earliest stages of breast cancer.

Cell blocks of breast FNAs frequently allow diagnosis of invasion or histological classification of proliferative changes.

Two major limitations of breast fine needle aspiration (FNA) compared with core needle biopsies (CNB) are the inability to determine whether a cancer is invasive and to classify proliferative lesions. We studied 40 consecutive "rapid cell blocks" from breast FNAs with surgical pathology follow-up to test whether cell blocks can overcome these limitations. Of 25 carcinomas, invasion could be identified in the cell block sections in 11 (44%). One cystosarcoma phyllodes was suspected based on the cell block sections. Cell blocks from 12 of 14 benign breast FNAs showed sufficient cells to assign a histologic diagnosis of no hyperplasia (1 case, confirmed on follow-up) and usual hyperplasia (11 cases; confirmed in eight of 11 on follow-up). Specific histologic diagnoses included intraductal papilloma (2 cases), and in situ lobular neoplasia (2 cases). Cell blocks complement smears and monolayers and appear to overcome major limitations of breast FNA.

Id-1 overexpression in invasive ductal carcinoma cells is significantly associated with intratumoral microvessel density in ER-negative/node-positive breast cancer.

The aim of this study is to investigate the possible role of inhibitor of DNA binding (Id-1) overexpression in human breast cancer. We examined Id-1 expression by immunohistochemistry in 263 human breast cancers, 15 in situ lesions and 248 invasive cancers to investigate the relationship between its expression and various clinicopathological factors. Id-1 expression was significantly higher in invasive ductal carcinoma than in in situ ductal carcinoma or other invasive cancer subtypes (P=0.029 and 0.006, respectively). We also examined the association between Id-1 expression and tumor angiogenesis by measuring microvessel densities (MVD). Regarding the endothelial cells of microvessels showed negative or very weak Id-1 expression, Id-1 overexpression was found to be significantly related to MVD (P=0.014). Furthermore, Id-1 overexpression was found to be significantly associated with higher MVD in the ER-negative and node-involved subgroups of breast cancer (P=0.040 and 0.046, respectively). These data indicate that Id-1 overexpression is significantly associated with tumor angiogenesis, especially in the ER-negative and node-positive subtypes of invasive breast cancer. Thus, Id-1 presents a possible therapeutic antitumor target molecule in ER-negative and node-positive breast cancer.

Long-term morbidity of patients with early breast cancer after sentinel lymph node biopsy compared to axillary lymph node dissection.

BACKGROUND AND OBJECTIVES: Sentinel lymph node biopsy (SLNB) is widely accepted as an excellent method in the management of early breast cancer in patients with clinically negative axillary lymph nodes. Since SLNB requires less traumatic surgery to the axilla than axillary lymph node dissection (ALND), it was assumed to result in reduced shoulder/arm morbidity. However, data on long-term morbidity after SNLB are sparse. The present study was set up to compare long-term arm/shoulder morbidity as well as oncological outcome after SLNB versus ALND in patients with early breast cancer. METHODS: Oncological outcome, objective shoulder/arm morbidity, and subjective complaints after SLNB or ALND for T1 breast cancer were assessed after a minimum follow-up of 20 months. RESULTS: One hundred thirty four patients were included in the study. Thirty-one patients underwent SNLB only, 103 patients had SLNB followed by ALND or ALND only. Loss of strength and hypaesthesia were less frequent after SLNB. No lymph oedema occurred after SNLB without adjuvant radiotherapy. Subjective complaints concerning pain, hypaesthesia, and paresthesia were more common in the ALND group. No axillary recurrence developed in either group. CONCLUSIONS: Isolated SLNB in node-negative pT1 breast cancer patients is a highly efficient tool to reduce postoperative long-term morbidity without compromising the local control of the disease. The reported ameliorations should favour SLNB as staging and treatment modality in patients suffering from early breast cancer.

Inter- and intra-ethnic differences for female breast carcinoma incidence in the continental United States and in the state of Hawaii.

BACKGROUND: Ethnic diversity is well-documented for female breast carcinoma incidence in the continental US but is not so well-established in the state of Hawaii. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) program, we analyzed n=323,607 in situ and invasive female breast cancer cases for major ethnic groups in the continental US and in Hawaii, diagnosed during the years 1992-2002. RESULTS: In the continental US, age-specific incidence rate patterns and prognostic factor profiles were good-risk for Asian or Pacific Islanders (API), intermediate for Whites, and poor-risk for Blacks. For example, early age-at-onset, high nuclear grade, aggressive histopathologic subtypes, and hormone receptor negative expression was associated with Black race in the continental US. In Hawaii, age-specific rate and prognostic profiles were more favorable for API than for White women, albeit not so striking as in the continental US. CONCLUSION: We observed inter- and intra-ethnic differences for female breast carcinoma in the continental US and in the state of Hawaii. While inter-racial disparities were expected, intra-racial differences were somewhat unexpected and possibly due to variations in racial subgroup mixing and/or cultural assimilation. For example, API women with breast carcinoma in the continental US included 96.03% Asians and 2.4% Pacific Islanders. In contrast, API women with breast carcinoma in Hawaii included 76.52% Asians and 23.46% Pacific Islanders. Moreover, APIs were more likely to be first-generation migrants in the continental US ( approximately 92%) than in Hawaii ( approximately 34%). Future studies should attempt to disaggregate racial data to separately characterize epidemiological patterns for individual ethnic groups.

Effects of breast-conserving therapy on lactation after pregnancy.

BACKGROUND: As the incidence of breast-conserving therapy in women of childbearing years increases, patient concerns regarding subsequent pregnancies and lactation have become more prevalent. There is a paucity of data regarding lactation outcomes in women who have undergone breast-conserving therapy and then sustained full-term pregnancies. Our objective was to evaluate lactation outcomes in patients with early-stage breast cancer treated with breast-conserving therapy. METHODS: We reviewed a database of over 3,000 patients treated from 1965 to 2003 to identify our cohort of premenopausal women who underwent breast-conserving therapy and subsequently sustained full-term pregnancies. Lactation outcome parameters (breast swelling, ability to lactate, and volume of lactation in the treated and untreated breasts) were the main outcome measures. RESULTS: We identified 28 pregnancies in 21 patients. The median age at diagnosis was 32 years. One patient underwent bilateral breast treatment; therefore, a total of 22 breasts were irradiated. All patients interviewed reported little or no swelling of the treated breast during pregnancy. Of the patients studied, 4 (18.2%) elected pharmacological suppression of lactation. Of the remaining 18 breasts, lactation occurred in 10 (55.6%), did not occur in 7 (38.9%) and was unknown for 1 (5.5%). The volume was reported as significantly diminished in 80% of breasts treated. Lactation in the contralateral breast occurred in all patients who did not undergo pharmacological suppression. CONCLUSION: Patients can experience successful lactation in the contralateral, untreated breast after breast-conserving therapy. In the treated breast, functional lactation is possible but is significantly diminished in the majority of patients.

Immunohistochemical biomarkers in patients with early-onset breast carcinoma by tissue microarray.

UNLABELLED: Young women with breast cancer have a poor prognosis, and the role of biologic markers in young women is not well defined. We investigated the association of estrogen receptor, progesterone receptor, Bcl-2, HER-2/neu, p53, and Ki-67 with clinicopathologic features and outcome in young women with breast cancer. METHODS: A cohort of 103 patients with early-onset breast cancer treated with conservative surgery and radiotherapy were entered in this study. Age range was 25-45 years, and median follow-up was 8.7 years. Each of the paraffin-embedded specimens was immunologically stained for six biomarkers expression by a recently developed tissue microarray method. RESULTS: The 10-year overall breast relapse-free and distant relapse-free survival rates were 82.7%, 84.6.4%, and 66.7%, respectively, with 14 local relapses and 26 distant metastases among the 103 patients evaluated. Positive expression of estrogen receptor, progesterone receptor, bcl-2, HER-2/neu, p53, and Ki-67 were 42.7%, 48.5%, 35.6%, 28.0%, 36.9%, and 39.7%, respectively. Tumor stage and nodal status were significantly associated with overall survival and distant metastasis-free rate in univariate and multivariate analysis. Progesterone receptor negativity and Ki-67 positivity were associated with distant metastasis. There was no statistically significant correlation between the six biomarkers and local relapse. CONCLUSIONS: Progesterone receptor, Ki-67, tumor stage, and nodal status were prognostic factors for distant failure in early-stage breast cancer in young patients. Further studies are needed to find other biologic markers associated with local failure in this group of patients.

Clinical characteristics of different histologic types of breast cancer.

Breast cancer is a heterogeneous disease, though little is known about some of its rarer forms, including certain histologic types. Using Surveillance, Epidemiology, and End Results Program data on 135 157 invasive breast cancer cases diagnosed from 1992 to 2001, relationships between nine histologic types of breast cancer and various tumour characteristics were assessed. Among women aged 50-89 years at diagnosis, lobular and ductal/lobular carcinoma cases were more likely to be diagnosed with stage III/IV, > or =5.0 cm, and node-positive tumours compared to ductal carcinoma cases. Mucinous, comedo, tubular, and medullary carcinomas were less likely to present at an advanced stage. Lobular, ductal/lobular, mucinous, tubular, and papillary carcinomas were less likely, and comedo, medullary, and inflammatory carcinomas were more likely to be oestrogen receptor (ER) negative/progesterone receptor (PR) negative and high grade (notably, 68.2% of medullary carcinomas were ER-/PR- vs 19.3% of ductal carcinomas). In general, similar differences were observed among women diagnosed at age 30-49 years. Inflammatory carcinomas are associated with more aggressive tumour phenotypes, and mucinous, tubular, and papillary tumours are associated with less aggressive phenotypes. The histologic types of breast cancer studied here differ greatly in their clinical presentations, and the differences in their hormone receptor profiles and grades point to their likely different aetiologies.

Dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy is well tolerated and safe in high-risk early breast cancer.

OBJECTIVE: The feasibility of dose-dense sequential adjuvant chemotherapy with Adriamycin, paclitaxel and cyclophosphamide was evaluated. METHODS: Fifty-five high-risk breast cancer patients were enrolled. The following chemotherapy schedule was used: 4 x Adriamycin --> 4 x paclitaxel --> 4 x cyclophosphamide, q 2 weeks (Adriamycin, 60 mg/m2; paclitaxel, 200 mg/m2 over 3 h, and cyclophosphamide, 800 mg/m2). RESULTS: The dose intensity was 95.0, 99.8 and 97.4% of that planned for treatment with Adriamycin, paclitaxel and cyclophosphamide, respectively. During treatment with Adriamycin, paclitaxel and cyclophosphamide, 20, 12.7 and 25.5% of the patients, respectively, did not need filgrastim to maintain the dose density. The average number of filgrastim doses per cycle, when necessary, was 3.6. Neutropenia of grade 3-4 was found in 67.3, 13.5 and 10.0% of the patients after treatment with Adriamycin, paclitaxel and cyclophosphamide, respectively. A single case of febrile neutropenia was observed. Anemia occurred in 96.4% of the patients, and was significantly more frequent (p = 0.031) and more severe (p = 0.002) during paclitaxel treatment than in the other chemotherapy cycles. CONCLUSIONS: Dose-dense sequential chemotherapy with Adriamycin, paclitaxel and cyclophosphamide is well tolerated and safe. Individual treatment with granulocyte colony-stimulating factor is needed to maintain the dose density in most patients, but some tolerate this regimen without it, probably due to differences in drug clearances.

A phase II study on the safety and efficacy of 5-fluorouracil, epirubicin, cyclophosphamide (FEC) followed by paclitaxel in the adjuvant treatment of breast cancer.

The incorporation of a taxane into an anthracycline-containing regimen in the adjuvant treatment of breast cancer is a promising approach. In this study, we aimed to evaluate the safety and efficacy of four cycles of FEC (fluorouracil 500 mg/m2, epirubicin 70 mg/m2, cyclophosphamide 500 mg/m2, every 3 weeks) followed by four cycles of paclitaxel (175 mg/m2 every 3 weeks) in the adjuvant treatment of node-positive and other high-risk breast cancer patients. A total of 88 female patients were enrolled. Mean age (+/- SD) of the patients was 47 +/- 10 (min: 24; max: 71). The patients were followed for a median of 48 months (min: 20; max: 64). The most common side effects were nausea-vomiting (grade I-II: 91%; grade III: 2%), as well as hematological toxicity (grade I-II: 70%; grade III: 3%). Although all patients experienced some degree of toxicity, it was severe enough to be classified as grade III or IV in only 10 (11%) of the cases. Of note, six (8%) patients had grade I and only one (1%) had grade II cardiotoxicity. No grade III or IV cardiotoxicity was observed. The full eight cycles of study treatment could be administered to 75 patients (85%). Side effects necessitated the reduction of the doses of FEC and paclitaxel in one (1%) and three patients (3%), respectively. Median overall (OS) and disease-free survival (DFS) have not yet been reached. Five-year OS and DFS have been estimated to be 78% and 61%, respectively. We conclude that FEC followed by paclitaxel is a well-tolerated and feasible regimen in the adjuvant treatment of early breast cancer. Its efficacity is comparable with other commonly used regimens and merits evaluation in a phase III study.