Endometrial brush cytology in the surveillance of post-menopausal patients under tamoxifen: a prospective longitudinal study.

OBJECTIVE: To evaluate cytological sampling of endometrium using Endobrush (Lab CCD, Paris, France) in the surveillance of tamoxifen-treated patients. STUDY DESIGN: Between February 1995 and October 1997, 687 tamoxifen-treated patients had serial ultrasound screening for endometrial pathology. In case of endometrial double layer thickness of more than 8mm, a cytological examination of endometrium was attempted followed by hysteroscopy and curettage. RESULTS: One hundred and eighty-nine patients had abnormal endometrial ultrasound findings. Cytological smear was not obtained in 39 patients because of cervical stenosis or pain in 33 and 6 cases, respectively. One hundred and fifty patients had cytological endometrial sampling followed by hysteroscopy and curettage. Cytological and histological findings correlated well in 145 cases (141 benign lesions and 4 endometrial cancers). There were five false positive (four atypia and one cancer). All patients remained free of endometrial cancer at 5 years follow-up. CONCLUSION: In tamoxifen-treated patients, endometrial cytology was reliable for detection of endometrial pathology, and was well accepted by the patients.

[A follow-up study about 52 cases of atypical lobular hyperplasia and lobular carcinoma in situ of the breast].

OBJECTIVE: To evaluate the biological behavior and treatment method for the breast atypical lobular hyperplasia (ALH) and breast lobular carcinoma in situ (LCIS). METHODS: Seventeen cases of ALH and thirty-five cases of LCIS were reviewed from July 1982 to January 1996. All cases were followed by physical examination, mammography and B-ultrasound for an average of 146.6 months (range, 3 - 257 months). RESULTS: Most cases of ALH and LCIS occurred before menopause (about 69.2%). Fifty-two cases of ALH and LCIS were occasionally verified pathologically after surgery for benign diseases. The microcalcification with ALH and LCIS had been detected in 25 cases, accounted for 48.1%. Eight cases of ALH/LCIS became invasive carcinoma. There were 5 cases in the same breast, 3 cases in the contralateral breast; The subsequent breast cancer occurred longer than nine years after ALH/LCIS was diagnosed. The family history of breast carcinoma and ovary carcinoma occurred in 4 cases of breast carcinoma, accounted for 50%, but it was no significant (P > 0.05). Also, there was no difference between LCIS and ALH, which occurred the breast carcinoma (P > 0.05). CONCLUSION: The excisional biopsy might be necessary to ALH and LCIS.

[Dual effects of androgens on mammary gland]. / Effet dual des androgènes sur la glande mammaire.

Androgens have a dual effect on mammary cells. Indeed, they have an influence on mammary cells proliferation thanks to several possible mechanisms, including their transformation into dihydrotestosterone (5alpha-reductase pathway) or into estradiol (aromatase pathway) or their binding to the androgen receptor (AR) and/or to the estrogen receptor (ER). Androgen signaling, using 5alpha-reductase pathway, enables the control of cell proliferation, mediated by AR. So androgen signaling plays a crucial role in breast homeostasis, negating the proliferative effects of estrogen signaling in the breast. When androgens transform into estrogens (aromatase pathway), they increase cell proliferation and mammary carcinogenesis risk. High levels of androgens and estrogens in the serum are associated with increased incidence of postmenopausal breast cancers. Genetic variations in metabolic genes (CYP11, CYP19) and in the AR gene are both involved in dual effects of androgens. Since mammary cells metabolic enzymes vary with time, aging increases the risk of breast cancer induced by estrogens and androgens. In addition, AR function can be perturbed by low doses of synthetic progestin, acting as endocrine disruptors to negate the protective effects of androgen signaling in the breast. In the future, the determination of AR expression in infiltrative breast cancer specimens and circulating androgens levels could provide additional information about hormonal dependency and prognosis of breast carcinomas.

[Premature ovarian failure after chemotherapy for breast cancer]. / Insuffisance ovarienne après chimiothérapie pour cancer mammaire.

About a quarter of breast cancers occur before menopause. Most breast cancer types occurring in young women require adjuvant treatments that can partially or definitively affect the reproductive function. Risk factors of chemotherapy-induced ovarian failure (CIOF) include woman's age, type, dose and schedule of chemotherapy. Cyclophosphamide-based regimens, notably when high doses are used, confer the highest rates of CIOF (especially for patients older than 40). A continual decline in ovary function follows cyclophosphamide-based regimens. By contrast, anthracycline-based regimens confer lower rates of CIOF and ovarian function recovers in half of the cases. The role of more recently reported adjuvant chemotherapy strategies in CIOF, such as alternative schedules (for example, dose-dense therapy), newer agents (for example, taxanes) or the addition of new therapies such as trastuzumab, is still controversial or unknown. Ovarian suppression through gonadotropin releasing hormone (Gn-RH) agonists treatment during chemotherapy to avoid CIOF is still under evaluation. Until the publication of prospective clinical trials results, "non-controlled" use of Gn-RH agonists should not be encouraged, notably for patients with a hormonosensible tumor, since there is insufficient evidence regarding their safety and effectiveness on female fertility preservation. More recent data suggest that an individual woman's risk of developing CIOF could be determined by the exploration of some genetic variants like CYP2C19. Before treatment strategy determination, the desire to preserve fertility should be systematically taken into account. Likewise, the early loss of ovarian function induced by treatments has to be explained to young patients diagnosed with a breast cancer and can sometimes lead to therapeutic options associated with less ovary dysfunction.

Infiltrative breast cancer during pregnancy and conservative surgery.

Mastectomy is considered as the standard therapy for gestational breast cancer. Since radiation therapy is harmful for the fetus, conservative surgery is rarely used during pregnancy. Among 16 patients with gestational breast cancer, 10 and 6 were treated with conservative surgery and mastectomy, respectively. No local recurrences occurred with a median follow-up time of 87 months. Among the 10 patients treated with conservative surgery, 3 chose therapeutic abortion and 7 opted to continue their pregnancy. Concerning these 7 fetuses, there were no congenital anomalies, nor growth restriction. All children were normal physically and neurologically. We concluded that conservative breast surgery may be an alternative to mastectomy in the treatment of gestational breast cancer and is safe for the fetus.

Improvement in intramammary sentinel lymph node removal using a novel prototype hand held probe during breast conservative surgery.

Intramammary sentinel lymph node excision during breast conservative surgery was performed, in this case report, using a prototype intraoperative gamma probe. In contrast to the four axillary sentinel lymph nodes that were subnormal, the excised intramammary sentinel lymph node was massively invaded by cancer cells. Therefore this finding had profound implication for the staging of the tumor and for treatment selection. This case report illustrates that an efficient intraoperative gamma probe is useful to locate and remove intramammary sentinel lymph node in breast cancer patients treated with breast conservation.

Randomized multicentric study of perioperative chemotherapy with mitoxantrone in early breast cancer.

BACKGROUND: To confirm the hypothesis that reducing the interval between surgery and adjuvant chemotherapy could improve prognosis, a randomized multicentric study of adjuvant perioperative chemotherapy (POC) in breast cancer was initiated. METHODS: A total of 552 patients were randomized to evaluate whether the addition of POC to standard adjuvant treatment significantly improved outcome. Patients were stratified according to menopausal status, with 362 patients in the postmenopausal group and 192 patients in the premenopausal group. Premenopausal women with positive axillary nodes, negative hormonal receptors, or grade 3 tumors received adjuvant mitoxantrone-based chemotherapy. Node-negative premenopausal patients with grade 1 or 2 tumors expressing hormonal receptors received no standard adjuvant treatment. All postmenopausal women received hormonal therapy (tamoxifen 20 mg/day for 3 years). The perioperative regimen was a 14 mg/m(2) mitoxantrone infusion at the end of tumor excision. RESULTS: With a median follow-up of 6.1 years, this study showed no significant advantage of POC on overall survival, disease-free survival, or metastasis-free survival for the total cohort or for the premenopausal and postmenopausal groups. CONCLUSIONS: POC was a safe procedure in this study. However, the addition of POC to standard adjuvant treatment offered no benefit in breast cancer adjuvant treatment.