Double blind randomized controlled trial of efficacy of ormeloxifene for the treatment of fibroadenoma (The FIBROCENT study).

BACKGROUND: We evaluated the effectiveness of Ormeloxifene (Centchroman) on regression of Fibroadenoma in a double-blind randomized controlled trial. METHODS: Patients with biopsy proven Fibroadenoma were enrolled between March 2023 and October 2023 and divided in two arms- Ormeloxifene group and Placebo group. Effectiveness of the treatment was evaluated using USG. No residual mass was defined as complete regression and more than 30% decrease in size was considered as partial regression. RESULTS: A total of 130 consecutive patients with Fibroadenoma were randomized to Ormeloxifene group (n = 65) and Placebo Group (n = 65). Complete regression was observed in 9% (6/65) patients in Ormeloxifene group and 10.8% (7/65) in Placebo Group at the end of 12 weeks (p = 0.49). Twenty one patients taking Ormeloxifene reported adverse events as compared to none in the other group. CONCLUSION: In our study Ormeloxifene was not found to be effective in treatment of fibroadenoma and had concerning side effects.

Single cell profiling of female breast fibroadenoma reveals distinct epithelial cell compositions and therapeutic targets.

Fibroadenomas (FAs) are the most common breast tumors in women. No pharmacological agents are currently approved for FA intervention owing to its unclear mechanisms and a shortage of reproducible human models. Here, using single-cell RNA sequencing of human FAs and normal breast tissues, we observe distinct cellular composition and epithelial structural changes in FAs. Interestingly, epithelial cells exhibit hormone-responsive functional signatures and synchronous activation of estrogen-sensitive and hormone-resistant mechanisms (ERBB2, BCL2 and CCND1 pathways). We develop a human expandable FA organoid system and observe that most organoids seem to be resistant to tamoxifen. Individualized combinations of tamoxifen with ERBB2, BCL2 or CCND1 inhibitors could significantly suppress the viability of tamoxifen-resistant organoids. Thus, our study presents an overview of human FA at single-cell resolution that outlines the structural and functional differences between FA and normal breast epithelium and, in particular, provides a potential therapeutic strategy for breast FAs.

Metformin as a new option in the medical management of breast fibroadenoma; a randomized clinical trial.

BACKGROUND: Fibroadenoma (FA) is the most common benign solid breast mass in women, with no definite method of management. Because fibroadenoma is dependent on female sex hormones and comprises hypertrophic changes at cellular levels, we investigated the effects of metformin (MF), a safe hypoglycemic agent with anti-estrogenic and anti-proliferative properties, in the management of fibroadenoma. METHODS: In this randomized clinical trial study, eligible women with fibroadenomas were assigned randomly to the metformin (1000 mg daily for six months) or the placebo group. Breast physical and ultrasound exam was performed before and after the intervention, and the changes in the size of fibroadenomas were compared in the two groups. RESULTS: Overall, 83 patients in the treatment, and 92 in the placebo group completed the study. A statistically significant difference in changing size between the two groups was observed only in the smallest mass. In the largest FAs, the rate of size reduction was higher in the treatment group (60.2 % vs. 43.5 %); while a higher rate of enlargement was observed in the placebo group (38 % vs. 20.5 %). In the smallest FAs, the rate of the masses that got smaller or remained stable was about 90 % in the treatment group and 50 % in the placebo group. We categorized size changes of FAs into < 20 % enlargement and ≥ 20 % enlargement. The odds ratio (OR) for an elargemnt less than 20% was 1.48 (95 % CI = 1.10-1.99) in the treatment group in comparison with the placebo group; the odds for an enlargement less than 20% was higher in women with multiples fibroadenomas (OR = 4.67, 95 % CI: 1.34-16.28). In our study, no serious adverse effect was recorded, and the medicine was well-tolerated by all users. CONCLUSIONS: This is the first study that evaluates the effect of MF on the management of fibroadenoma, and the results suggest a favorable effect. Larger studies using higher doses of MF and including a separate design for patients with single or multiple FAs are suggested in order to confirm this effect. TRIAL REGISTRATION: This trial (IRCT20100706004329N7) was retrospectively registered on 2018-10-07.

[A Case of Lobular Carcinoma In Situ Occurring in a Fibroadenoma of the Breast].

The patient was a 43-year-old premenopausal woman with a 14×11 mm tumor in upper outer quadrant of the left breast, diagnosed as a fibroepithelial lesion using core needle biopsy. Resection was performed. Histopathologically, the resected specimen was diagnosed as a fibroadenoma with lobular carcinoma in situ(LCIS). Tamoxifen was administered as endocrine therapy to reduce recurrence risk. We report a case of LCIS accidentally discovered by surgical resection of a benign tumor.

A randomized trial of Boswellia in association with betaine and myo-inositol in the management of breast fibroadenomas.

OBJECTIVE: Breast fibroadenoma is a common finding in young women and actually accounts for the majority of benign breast lumps. Fibroadenoma does not require any treatment unless clinical symptoms (mostly mastalgia) or histological markers of cancer risk (atypia) impose specific medical or surgical intervention. In symptomatic fibroadenoma, anti-estrogenic treatments provided evidence of success. Yet, these therapies are often associated with relevant side effects that lead to drug treatment discontinuation. Additionally, in such cases, relapse is a frequent issue. Therefore, an optimal strategy is still warranted. Boswellia, betaine and myo-inositol have already been proved to modulate different pathways - inflammatory, metabolic, oxidative and endocrine processes - in a wide array of human tissues. Based on that background, we hypothesized that these substances can effectively synergize in inducing the regression of fibroadenoma. PATIENTS AND METHODS: We included 64 patients ≤ 30 years of age with fibroadenoma. The patients were randomized into two groups. The experimental group was treated with an association of Boswellia, betaine, myo-inositol, B-group vitamins and N-acetylcysteine for 6 months; otherwise, the placebo group was treated only with B-group vitamins and N-acetylcysteine. Patients were monitored at the enrollment and the end of the study for evaluating the clinical response. RESULTS: A significant clinical improvement was observed in the experimental arm. Fibroadenoma median volume reduction averaged 17.86% in the experimental group and 5.96% in the placebo group. Moreover, 14 out of 36 (38.88%) patients showed a reduction of fibroadenoma volume compared to 5/28 (17.85%) observed in the placebo group (p = 0.005). CONCLUSIONS: A supplementation with Boswellia, betaine and myo-inositol reduces fibroadenoma dimension in young women. No relevant side effects have been recorded.

Patología mamaria en niñas y adolescentes: a propósito de un caso / Breast pathology in adolescents: case report

La patología mamaria en el grupo de niñas y adolescentes es poco frecuente, correspondiendo generalmente a lesiones benignas, sin embargo, crea gran ansiedad en la paciente y su grupo familiar .El propósito del presente artículo es en base a un caso clínico larevisión de la patología mamaria benigna más frecuente en este grupo etario, las imágenes y su tratamiento...

Pediatric and adolescents breast masses are relatively rare, and most are benign, nevertheless, is very disconcerting in the patient and her family. The purpose of this article is based on a case review the benign breast conditions, the imaging findings and treatmentstrategies in this population...

Evolución inusual de fibroadenomas mamarios múltiples en adolescente con metrorragia disfuncional / Unusual evolution of multiple breast fibroadenomas in adolescent with dysfunctional uterine bleeding

Se describe la inusual evolución de fibroadenomas (FA) mamarios múltiples en una adolescente de 11 años en tratamiento con progestinas cíclicas por metrorragia disfuncional. Inicialmente la ecografía mamaria mostró más de 10 lesiones sólidas en cada mama de hasta 2,6 cm, compatibles con fibroadenomas. Al cabo de 13 meses las lesiones se redujeron en número y tamaño. Se discute la historia natural de los FA, la influencia hormonal en la etiología de los FA y finalmente el diagnóstico ecográfico y manejo de este cuadro en la adolescencia. Se plantea, a modo de hipótesis, que existe un desbalance estrógeno-progesterona (E-P) dado por ciclos anovulatorios en el periodo posmenárquico, que se manifestó con metrorragia disfuncional y la presencia de FA. Al administrar progesterona cíclica se reequilibra la relación E-P explicando el control del ciclo y la involución de las lesiones mamarias.

We describe the unusual evolution of multiple fibroadenomas (FA) in a 11-years old adolescent during treatment of an abnormal uterine bleeding with cyclic progestins. Inicially ultrasound demonstrated more than 10 masses in each breast, up to 2,6 cm diameter, compatible with fibroadenomas. After 13 month follow up lesions decreased in number and size. We discuss the natural history of FA, the hormonal influence in FA etiology, the ultrasound diagnosis and the managment of this pathology in adolescents. We hypothesized that there is an estrogen/progestin imbalance, due to the anovulatory cycles of the post menarche period that caused the AUB and FA. Cyclic progesterone balanced the E/P relation, thus managing both AUB and causing regression of the breast masses.

Unusual aggressive breast cancer: metastatic malignant phyllodes tumor.

For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. While most invasive primary breast cancers are epithelial derived adenocarcinomas, rare neoplasms such as the phyllodes tumor may arise from mesenchymal tissue. Compared to the breast adenocarcinoma, the phyllodes tumor tends to affect a younger population, follows a different clinical course, is associated with different imaging and histological findings and is managed distinctively. There may be difficulty in differentiating the phyllodes tumor from a large fibroadenoma, but the mammographer plays a key role in reviewing the clinical and imaging data in order to arrive at the correct diagnosis. Early diagnosis with proper surgical management can often cure non-metastatic phyllodes tumors. However, in rare cases where metastasis occurs, prognosis tends to be poor. This report describes the presentation, imaging findings and management of a metastatic malignant phyllodes tumor.

Expression of Ki-67 and Bcl-2 biomarkers in normal breast tissue from women of reproductive age treated with raloxifene.

OBJECTIVE: To evaluate the effect of raloxifene on antigen expression of Ki-67 and Bcl-2 in normal breast tissue. MATERIALS AND METHODS: A randomized, double-blind study was conducted with 40 premenopausal women aged 18-40 years who had been diagnosed with fibroadenoma of the breast. The patients were divided into two groups: Group A (placebo, n = 20), and Group B (raloxifene 60 mg, n = 20).The medication was taken for 22 days initiating from the first day of the menstrual cycle. An excisional biopsy was performed on the 23rd day. At the time of biopsy, a sample of normal breast tissue was collected to evaluate protein expression of Ki-67 and Bcl-2. The Student's t test and Chi-square test were used for statistical data analysis and the significance level was established at 5%. RESULTS: The mean percentage of nuclei stained for Ki-67 was 22.16 ± 1.91 (p < 0.001) and 2.161 ± 0.181 in the control group and the raloxifene group. The expression of Bcl-2 was similar in both groups (p = 0.8888). CONCLUSIONS: Raloxifene treatment significantly reduced antigen expression of Ki-67, but failed to have any significant results on the Bcl-2 expression. Further studies are warranted to evaluate the mechanism of raloxifene on apoptosis in normal breast tissue.

Monitoring the response to primary medical therapy for breast cancer using three- dimensional time-resolved optical mammography.

Primary medical therapy is used to reduce tumour size prior to surgery in women with locally advanced breast cancer. Optical tomography is a functional imaging technique using near- infrared light to produce three-dimensional breast images of tissue oxygen saturation and haemoglobin concentration. Its advantages include the ability to display quantitative physiological information, and to allow repeated scans without the hazards associated with exposure to ionising radiation. There is a need for a non-invasive functional imaging tool to evaluate response to treatment, so that non-responders can be given the opportunity to change their treatment regimen. Here, we evaluate the use of optical tomography for this purpose. Four women with newly diagnosed breast cancer who were about to undergo primary medical therapy gave informed and voluntary consent to take part in the study. Changes in physiological and optical properties within the tumour were evaluated during the course of neoadjuvant chemotherapy. Optical imaging was performed prior to treatment, after the first cycle of chemotherapy, halfway through, and on completion of chemotherapy. Images of light absorption and scatter at two wavelengths were produced, from which images of total haemoglobin concentration and oxygen saturation were derived. All patients that showed a good or complete response to treatment on MRI showed a corresponding recovery in the haemoglobin concentration images. Changes in mean tumour total haemoglobin concentration could be seen four weeks into treatment. The tumour oxygen saturation was low compared to background in three out of four patients, and also showed a return to baseline over treatment. Optical imaging of the breast is feasible during primary medical therapy and can be used to assess response to treatment over six months.

Evaluation of estrogen and progesterone receptors in non-neoplastic breast tissue of women of reproductive age exposed to tamoxifen and raloxifene: a randomized, double-blind study.

The objective of the present study was to compare the effects of tamoxifen and raloxifene in non-neoplastic breast epithelium. A randomized, double-blind study was carried out in 57 ovulatory, premenopausal women of 18-40 years of age, who had been diagnosed with fibroadenoma of the breast. The patients were divided into three groups: Group A: placebo, n=20; Group B: tamoxifen 20 mg/day, n = 21; and Group C: raloxifene 60mg/day, n=16. The study medication was given for 22 days starting on the first day of the menstrual cycle. On the 23rd day, the fibroadenoma was removed and a sample of non-neoplastic breast tissue was collected for immunohistochemical evaluation of estrogen and progesterone receptors. Comparison between the mean percentages of stained nuclei in the three groups was performed by analysis of variance and multiple comparisons, using Tukey's method to compare pairwise means, with significance established at P < 0.05. Exposition to tamoxifen or raloxifene resulted in a significant and similar reduction in the mean percentage of stained nuclei for estrogen and progesterone receptors (P<0.0001). Tamoxifen and raloxifene reduce progesterone and estrogen receptor alpha expression significantly and to a similar extent in the non-neoplastic breast tissue of women of reproductive age.

Treatment of fibroadenomatosis in 14 cats with aglepristone - changes in blood parameters and follow-up.

Fourteen female cats with fibroadenomatosis were treated with aglepristone, and the effectiveness of the treatment and its effect on selected haematological and blood chemistry parameters were studied. The cats were monitored for 12 months after the end of the treatment. Complete remission of the clinical signs was achieved on average 3.9 weeks after the treatment began; the success of the treatment confirmed the clinical diagnosis of fibroadenomatosis. During the course of the treatment the cats' haematological parameters returned to normal. In cats that had previously been treated with long-acting medroxyprogesterone acetate, treatment with aglepristone for five weeks was recommended. Cases of fibroadenomatosis reappearing after a few months should be regarded as new disease rather than a relapse. Six cats were subsequently mated and four gave birth to one or more litters; all the pregnancies proceeded normally with no clinically evident fibroadenomatosis. The other eight cats underwent ovariohysterectomy soon after the aglepristone treatment was completed.

A breast fibroadenoma mimicking an extranodal deposit of Hodgkin's lymphoma in 67Ga imaging.

We present the case of a young woman with classical nodular sclerosing Hodgkin's lymphoma (clinical stage IIB). During staging work-up, intense gallium-67 ((67)Ga) accumulation in a left breast lump raised the suspicion of an extranodal deposit, but biopsy favoured a benign histology. A post-treatment (67)Ga scan showed complete remission of the disease with normal tracer uptake in the left breast. However, a few months after treatment, a faint left mammary concentration of (67)Ga was observed. The breast mass was excised and histopathology was consistent with fibroadenoma. This unusual presentation is a new addition to the literature on false-positive (67)Ga findings and chemotherapy-associated tracer changes.

Importancia de la información en el control de los síntomas de la displasia mamaria / Importance of information in the control of the symptoms of breast dysplasia

INTRODUCCIÓN. La displasia mamaria es un problema de salud de gran repercusión social, por el estrés y la ansiedad que suelen acompañarla. El presente trabajo tuvo el objetivo de valorar diferentes variantes de conducta ante esta afección. MÉTODOS. Se realizó un estudio retrospectivo-prospectivo con 3668 pacientes diagnosticadas de displasia mamaria, y atendidas por esta razón entre enero de 1991 y diciembre de 2004 en el Hospital Universitario Comandante «Manuel Fajardo¼. RESULTADOS. La incidencia de displasia mamaria (enfermedad fibroquística) en la consulta de patología mamaria fue del 50 por ciento, seguida en frecuencia por el fibroadenoma y las enfermedades inflamatorias. Se realizó el estudio en dos etapas: una con carácter retrospectivo (1991-1996) y otra con carácter prospectivo (1997-2004). La evolución de los casos que solo recibieron información fue similar a la de los pacientes que fueron sometidos a otros esquemas de tratamiento médico, en ambas etapas. Se necesitó exéresis quirúrgica en el 16,21 por ciento y 13,42 por ciento de los pacientes, respectivamente, a causa de dudas en relación con un carcinoma. CONCLUSIONES. La información médica es una opción que puede utilizarse en más del 70 por ciento de las mujeres que presentan displasia mamaria (enfermedad fibroquística). Tiene la ventaja de que los resultados son más duraderos que los del tratamiento médico, y de que disminuye el consumo innecesario de medicamentos. El tratamiento quirúrgico de la enfermedad fibroquística está solo justificado ante la duda de cáncer y en lesiones que no se modifican ni duelen durante el ciclo menstrual, sobre todo en el caso de mujeres mayores de 35 años(AU)

INTRODUCTION. Breast dysplasia is a health problem of great social impact due to the stress and anxiety accompanying it. The present paper was aimed at assessing different variants of behavior before this affection. METHODS. A retrospective prospective study was conducted among 3 688 patients that were diagnosed breast dysplasia and received attention from January 1991 to December 2004 in «Comandante Manuel Fajardo¼ Teaching Hospital. RESULTS. The incidence of breast dysplasia (fibrocystic disease) at the breast pathology office was 50 percent, followed in frequency by fibroadenoma and inflammatory diseases. A two-stage study was undertaken: one with retrospective character (1991-1996) and the other with prospective character (1997-2004). The evolution of the cases that received only information was similar to that of those that underwent other medical treatment schemes, in both stages. Surgical exeresis was necessary in 16.21 percent and 13.42 percent of the patients, respectively, due to suspicion of carcinoma. CONCLUSIONS. Medical information is an option that may be used in more than 70 percent of females with breast dysplasia (fibrocystic disease). Some of its advantages are that the results last more than those of medical treatment and that it reduces the unnecessary administration of drugs. The surgical treatment of the fibrocystic disease is only justified when cancer is suspected and in lesions that neither modify nor hurt during the menstrual cycle, mainly in females over 35(AU)

[Expression of Bax protein in normal tissue of premenopausal women treated with raloxifene]. / Expressão da proteína Bax no tecido mamário normal de mulheres no menacme tratadas com raloxifeno.

PURPOSE: to evaluate the expression of Bax antigen in the normal mammary epithelium of premenopausal women treated with raloxifene. METHODS: a randomized double-blind study was conducted in 33 ovulatory premenopausal women with fibroadenoma. Patients were divided into two groups: Placebo, (n=18) and Raloxifene 60 mg, (n=15). The medication was used for 22 days, beginning on the first day of the menstrual cycle. An excisional biopsy was carried out on the 23rd day of the menstrual cycle and a sample of normal breast tissue adjacent to the fibroadenoma was collected and submitted to immunohistochemical study using anti-Bax polyclonal antibody to evaluate the expression of Bax protein. Immunoreaction for Bax was evaluated taking into consideration intensity and fraction of stained cells, whose combination resulted in a final score ranging from 0 to 6. Cases with a final score >3 were classified as positive for Bax. The c2 test was used for statistical analysis (p<0.05). RESULTS: the percentage of positivity of Bax protein expression was 66.7 and 73.3% in Groups A and B, respectively. There was no significant difference in Bax expression between the two groups (p=0.678). CONCLUSIONS: raloxifene, administered for 22 days in the dose of 60 mg/day, did not alter the expression of Bax protein in the breast normal tissue of premenopausal women.

Effect of oral contraceptive with and without associated estriol on ultrasound measurements of breast fibroadenoma: randomized clinical trial.

CONTEXT AND OBJECTIVE: Fibroadenomas are the most common benign tumors of the female breast. The aim of this study was to evaluate the proliferative activity of breast fibroadenoma as shown by ultrasound measurements, following administration of oral contraceptives with and without associated estriol. DESIGN AND SETTING: This was a randomized, double-blind, placebo-controlled clinical trial carried out in the Mastology Sector, Department of Gynecology, Universidade Federal de São Paulo. METHODS: We studied 33 women with fibroadenomas. Ten were placed in group 1 and took an oral contraceptive consisting of levonorgestrel and ethinyl estradiol together with placebo material in the same capsule, for four consecutive cycles with a seven-day interval between them. The other 23 patients constituted group 2 and took the oral contraceptive as above together with estriol in the same capsule, in the same way as done by the group 1 patients. We took ultrasound measurements of their tumors (in three dimensions) before and after the intake of medication. At the end of the study, all the patients had their tumors removed by surgery. RESULTS: We observed decreased fibroadenoma width among the users of oral contraceptives with placebo, and this decrease was statistically significant. In the other group, we did not observe any changes (in width, length or height). CONCLUSION: The results confirm that estriol may block the protective effect of oral contraceptives on fibroadenomas, since we observed decreased fibroadenoma width among the group 1 patients but not the group 2 patients.

Effect of oral contraceptive with and without associated estriol on ultrasound measurements of breast fibroadenoma: randomized clinical trial

CONTEXT AND OBJECTIVE: Fibroadenomas are the most common benign tumors of the female breast. The aim of this study was to evaluate the proliferative activity of breast fibroadenoma as shown by ultrasound measurements, following administration of oral contraceptives with and without associated estriol. DESIGN AND SETTING: This was a randomized, double-blind, placebo-controlled clinical trial carried out in the Mastology Sector, Department of Gynecology, Universidade Federal de São Paulo. METHODS: We studied 33 women with fibroadenomas. Ten were placed in group 1 and took an oral contraceptive consisting of levonorgestrel and ethinyl estradiol together with placebo material in the same capsule, for four consecutive cycles with a seven-day interval between them. The other 23 patients constituted group 2 and took the oral contraceptive as above together with estriol in the same capsule, in the same way as done by the group 1 patients. We took ultrasound measurements of their tumors (in three dimensions) before and after the intake of medication. At the end of the study, all the patients had their tumors removed by surgery. RESULTS: We observed decreased fibroadenoma width among the users of oral contraceptives with placebo, and this decrease was statistically significant. In the other group, we did not observe any changes (in width, length or height). CONCLUSION: The results confirm that estriol may block the protective effect of oral contraceptives on fibroadenomas, since we observed decreased fibroadenoma width among the group 1 patients but not the group 2 patients.

CONTEXTO E OBJETIVO: Fibroadenomas são os tumores benignos mais comuns na mama feminina. Avaliamos a atividade proliferativa do fibroadenoma mamário por medidas ultra-sonográficas após a administração de anticoncepcional hormonal combinado oral, associado ou não ao estriol. TIPO DE ESTUDO E LOCAL: Ensaio clínico randomizado, duplo-cego, placebo-controlado, realizado na Universidade Federal de São Paulo. MÉTODOS: Foram estudadas 33 pacientes portadoras de fibroadenoma, do setor de Mastologia da Disciplina de Ginecologia da Universidade Federal de São Paulo, sendo que 10 mulheres constituíram o grupo 1 e utilizaram anticoncepcional oral composto de levonorgestrel e etinilestradiol, associados a um comprimido de placebo, na mesma cápsula, por quatro ciclos consecutivos, com intervalo de sete dias entre os mesmos. As restantes 23 pacientes alocaram-se no grupo 2 e ingeriram, além do anticoncepcional oral descrito acima, um comprimido de estriol, que foi manufaturado conjuntamente ao anticoncepcional, em uma mesma cápsula, sendo utilizado da mesma forma que nas pacientes do grupo 1. Realizamos medidas ultra-sonográficas dos tumores (três dimensões) antes e após a ingestão da medicação. Ao término do estudo, as pacientes sofreram exérese de suas tumorações. RESULTADOS: Obtivemos diminuição da largura nos fibroadenomas de pacientes usuárias apenas de anticoncepcional oral e esse resultado foi estatisticamente significante. Não houve alteração de nenhuma dimensão (largura, altura ou comprimento) no outro grupo. CONCLUSÕES: Os resultados corroboraram que o estriol bloquearia o efeito protetor do anticoncepcional hormonal combinado oral sobre os fibroadenomas, já que observamos diminuição na largura dos fibroadenomas das pacientes do grupo 1 e não do grupo 2.

Expression of nm23, MMP-2, TIMP-2 in breast neoplasm in Zhengzhou Center Hospital, China.

BACKGROUND: In recent years, the carcinoma of the breast threatens to women's health heavily. Invasion and metastasis is the main reason that results in the patients death. OBJECTIVE: A prospective study is made in the center hospital of zhengzhou, in order to approach the expression of nm23, MMP-2 (Matrix metallo-proteinase-2), TIMP-2 (it's tissue-inhibitor of the metalloproteinase-2) in the breast neoplasm and the relationship with invasion and metastasis. METHODOLOGY: This study applied the immunohistochemistry technique SP method RESULTS: In fibroadenoma, ductal carcinoma in situ and invasive ductal carcinoma of the breast 4 groups, the positive immunostaining rate of nm23, MMP-2 and TIMP-2 have significant difference among 4 groups (p < 0.05). In the breast invasive ductal carcinoma, the expression of nm23 and TIMP-2 decreased or the expression of MMP-2 increased CONCLUSION: This suggested that invasion and metastasis is ability of the neoplasm. MMP-2 in the breast ductal carcinoma in situ appears of high expression and this suggested that the positive expression of this onco-proteins was the early incident in the genetic course of the breast cancer The unite detection of nm23, MMP-2 and TIMP-2 expression would contribute to the early diagnosis and prognostic assessment of the carcinoma of the breast.