Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy.

INTRODUCTION: The Objective was to investigate the incidence of lymphedema after breast cancer treatment and to analyze the risk factors involved in a tertiary level hospital. METHODS: Prospective longitudinal observational study over 3 years post-breast surgery. 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1-54 months). Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, shoulder range of motion limitation and local and systemic therapies were analyzed as possible risk factors for lymphedema. RESULTS: Most cases of lymphedema appeared in the first 2 years. 13.9% of patients developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92-18.16) and 3.9 (1.60-9.49) respectively. CONCLUSIONS: The main risk factors for lymphedema were the more radical surgeries (ALND and mastectomy). The risk associated with these procedures appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND lasting at least two years, in which special attention is paid to these risk factors, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

Long-term predictors of residual or recurrent cervical intraepithelial neoplasia 2-3 after treatment with a large loop excision of the transformation zone: a retrospective study.

OBJECTIVE: To assess the long-term risk factors predicting residual/recurrent cervical intraepithelial neoplasia (CIN 2-3) and time to recurrence after large loop excision of the transformation zone (LLETZ). DESIGN: Retrospective study. SETTING: Colposcopy clinic. POPULATION: 242 women with CIN 2-3 treated between 1996 and 2006 and followed up until June 2016. METHODS: Age, margins, and high-risk human papillomavirus (HR-HPV) were estimated using Cox proportional hazard and unconditional logistic regression models. The cumulative probability of treatment failure was estimated by Kaplan-Meier analysis. MAIN OUTCOME MEASURE: Histologically confirmed CIN 2-3, HR-HPV, margins, age. RESULTS: CIN 2-3 was associated with HR-HPV (HR = 30.5, 95% confidence interval [CI] = 3.80-246.20), age >35 years (HR = 5.53, 95% CI = 1.22-25.13), and margins (HR = 7.31, 95% CI = 1.60-33.44). HR-HPV showed a sensitivity of 88.8% and a specificity of 80%. Ecto+ /endocervical+ (16.7%), uncertain (19.4%) and ecto- /endocervical+ margins (9.1%) showed a higher risk of recurrence (odds ratio [OR] = 13.20, 95% CI = 1.02-170.96; OR = 15.84, 95% CI = 3.02-83.01; and OR = 6.60, 95% CI = 0.88-49.53, respectively). Women with involved margins and/or who were HR-HPV positive had more treatment failure than those who were HR-HPV negative or had clear margins (P-log-rank <0.001). CONCLUSIONS: HR-HPV and margins seem essential for stratifying post-LLETZ risk, and enable personalised management. Given that clear margins present a lower risk, a large excision may be indicated in older women to reduce the risk. TWEETABLE ABSTRACT: After LLETZ for CIN 2-3, recurrences appear more often in women with positive HR-HPV and involved margins and aged over 35.

Secretion and dual regulation between epidermal growth factor and transforming growth factor-beta1 in MDA-MB-231 cell line in 42-hour-long cultures.

MDA-MB-231 is a breast cancer cell line which possesses large quantities of epidermal growth factor (EGF) receptors and specific high-affinity transforming growth factor-beta1 (TGF-beta1) receptors. We have established that these cells secrete constitutively measurable levels of EGF and TGF-beta1 in conditioned medium. The constitutive secretion of EGF decreased over time in culture (42 h), while the constitutive secretion of TGF-beta1 remained constant. TGF-beta1 secretion in EGF-treated cells was lower than in controls (P < 0.0001), but EGF concentrations were not modified after TGF-beta1 supplement. We postulate that in MDA-MB-231 cell line there is a dual regulation between both growth factors.

Growth of MDA-MB-231 cell line: different effects of TGF-beta(1), EGF and estradiol depending on the length of exposure.

The human cell line MDA-MB-231 is a prototype for the study of hormone-independent breast cancer. Modification of cell growth behaviour has been observed after treating these cells with growth factors. EGF is a typical stimulatory growth factor for many cell types, whereas transforming growth factor beta(1)(TGF-beta(1)) acts with inhibitory character. Here we observed cell growth inhibition after EGF as well as after TGF-beta(1)treatments. Nevertheless, in the 42-h experiments, EGF-treated cultures grew before (18 hours) respect to the TGF-beta(1)and E(2)-treated cultures (24 h), and in the 11-day experiments, EGF-treated cultures started growing (7 days) after TGF-beta(1)-treated cultures (5 days). Estradiol inhibited the proliferation of these cells only after several days of treatment.

Estimation of the epidermal growth factor receptor by the hydroxyapatite method in human breast cancer.

Results of epidermal growth factor (EGF) receptor in human breast tumours show large variations, mainly due to the lack of standardization of the assays. Our EGF receptor values are higher than those reported previously which may be due to the use of the hydroxyapatite to separate bound and non-bound ligand in a radioligand assay. We found EGF receptors in 58% (103/178) of the tumours (EGF receptor levels: 3 to 625 fmol/mg of membrane protein, mean = 33.3, median = 17.4), with a median Kd of 0.642 nmol/l. There was an inverse correlation between EGF receptors and estrogen receptors (r = -0.215, p = 0.00002, Kendall correlation). There was a difference between EGF receptor content in grade II (mean = 16.9) and grade III tumours (mean = 59.3) (p = 0.027), but not between histopathological types and lymph node status. The relevance of EGF receptor largely depends on the reliability of its determination. The standardized EORTC methodology is a reproducible alternative which will expand EGF receptor determination and permit comparability of data between laboratories.

[The estrogen receptor/progesterone receptor quotient as an index of the transcriptional activity of estrogen receptors in breast cancer]. / El cociente receptores de estrógenos/receptores de progesterona como índice de la actividad transcripcional de los receptores de estrógenos en el cáncer de mama.

BACKGROUND: The aim of this study was to determine whether the induction of progesterone receptors (PR) for estrogen receptors (ER) in variable in breast cancer, whether it differs among pre and post menopausal women and whether the ER/PR quotient may be an index of tumoral biology. METHODS: The ER and PR content was determined by enzyme immunoassay in 814 breast tumors and the ER/PR quotient was calculated in the ER+PR+ tumors (n = 395). RESULTS: ER/PR values < 1 were more frequent in premenopausal women (66%) than in post menopausal women (38%). No influence was observed with regard to age. CONCLUSIONS: The highest ER/PR values were found in post menopausal women indicating decreased estrogen receptor transcriptional activity in this subgroup contrary to that found in premenopausal women.

Total and unbound cytosolic estrogen and progesterone receptors in myometrium and fibroid after gonadotropin-releasing hormone agonist treatment.

OBJECTIVE: To study the changes in bound and unbound cytosolic estrogen receptor (ER) and progesterone receptor (PR) in fibroid and myometrium after treatment with gonadotropin-releasing hormone agonists (GnRH-a). DESIGN: Prospective randomized study. SETTING: A tertiary institutional hospital. PATIENTS: Thirty premenopausal women with normal regular menstrual cycles and uterine fibroids. INTERVENTIONS: Patients were randomized to receive buserelin acetate for 3 months (n = 20) or no treatment (n = 10) before hysterectomy. MAIN OUTCOME MEASURES: Bound and unbound ER and PR. RESULTS: In nontreated women, values of unbound ER and PR in fibroid were higher than in myometrium. There were no differences in total receptors. The total and unbound ER in myometrium was higher in treated than in nontreated women. There were no differences in fibroid. CONCLUSIONS: The higher content of unbound hormone receptors in fibroid correlates with an exacerbation of the hormone dependence of this tissue compared with myometrium. The increase of total and unbound ER in myometrium after treatment suggests a higher level of synthesis or a lower level of degradation of receptors in this tissue.