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1.
J Surg Oncol ; 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32497273

RESUMO

OBJECTIVES: To identify the association between cording and breast cancer-related lymphedema (BCRL); describe time course, location, symptoms and functional impairments. METHODS: A total of 1181 patients were prospectively screened for BCRL after breast cancer (BC) surgery, including patient-reported outcome measures (4193) and perometric arm volume measurements (BCRL defined as relative or weight-adjusted volume change [RVC or WAC] ≥10% ≥3 months postoperatively). RESULTS: A total of 374/1181 patients (31.7%) reported cording first a median of 4.5 months postoperatively, and were more likely to: have body mass index less than 30 kg/m2 ; be less than 55 years of age; have had mastectomy, axillary lymph node dissection, regional lymph node radiation, neoadjuvant chemotherapy (all P < .001), or RVC/WAC ≥10% (P = .002). Patients who reported cording had 2.4 times the odds of developing BCRL compared to those who did not (odds ratio = 2.40; 95% confidence interval = 1.40-4.11; P = .002), and most frequently reported these symptoms: tenderness (61.2%), aching (60.7%), and firmness/tightness (59.8%). On multivariable analysis, cording was significantly correlated with functional difficulty for 17 actions. CONCLUSIONS: Patients frequently present with cording, potentially months after BC surgery. Risk factors for and symptoms of cording are identified, and treatment is recommended. Patients reporting cording are at higher risk of BCRL, therefore, cording should be incorporated into BCRL risk stratification.

2.
J Neuroendocrinol ; 31(8): e12760, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31233647

RESUMO

Oxytocin (OT) often regulates social behaviours in sex-specific ways, and this may be a result of sex differences in the brain OT system. Adult male rats show higher OT receptor (OTR) binding in the posterior bed nucleus of the stria terminalis (pBNST) than adult female rats. In the present study, we investigated the mechanisms that lead to this sex difference. First, we found that male rats have higher OTR mRNA expression in the pBNST than females at postnatal day (P) 35 and P60, which demonstrates the presence of the sex difference in OTR binding density at message level. Second, the sex difference in OTR binding density in the pBNST was absent at P0 and P3, but was present by P5. Third, systemic administration of the oestrogen receptor (ER) antagonist fulvestrant at P0 and P1 dose-dependently reduced OTR binding density in the pBNST of 5-week-old male rats, but did not eliminate the sex difference in OTR binding density. Fourth, pBNST-OTR binding density was lower in androgen receptor (AR) deficient genetic male rats compared to wild-type males, but higher compared to wild-type females. Finally, systemic administration of the histone deacetylase inhibitor valproic acid at P0 and P1 did not alter pBNST-OTR binding density in 5-week-old male and female rats. Interestingly, neonatal ER antagonism, AR deficiency, and neonatal valproic acid treatment each eliminated the sex difference in pBNST size. Overall, we demonstrate a role for neonatal ER and AR activation in setting up the sex difference in OTR binding density in the pBNST, which may underlie sexual differentiation of the pBNST and social behaviour.

3.
Breast Cancer Res Treat ; 175(3): 649-658, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30919166

RESUMO

PURPOSE: This study evaluated development of edema in patients receiving PI3K/mTOR/CDK4/6 targeted therapy for metastatic breast cancer (MBC). METHODS: We reviewed medical records of 160 patients receiving targeted therapy with PI3K/mTOR/CDK4/6 inhibitors to treat MBC (n = 160; 185 treatment occurrences). Clinicopathologic data, treatment details, and edema incidence were recorded. RESULTS: Edema incidence was 43.1% (69/160) overall and 25.6% (41/160) in the upper extremity ipsilateral to the treated breast. In 185 therapy regimens administered, 6.8% of patients on a PI3K inhibitor, 8.8% of patients on an mTOR inhibitor, and 9.2% of patients on a CDK4/6 inhibitor experienced new onset or worsened preexisting upper extremity edema. Further, 9.1% of patients on a PI3K inhibitor, 18.8% of patients on an mTOR inhibitor, and 10.5% of patients on a CDK4/6 inhibitor experienced new onset or worsened preexisting edema elsewhere in the body. Multivariate logistic regression showed that, beyond the established breast cancer-related lymphedema (BCRL) risk factors [axillary lymph node dissection (Odds Ratio (OR) 2.69, p = 0.020), regional lymph node irradiation (OR 6.47, p < 0.001), and body-mass index ≥ 30 kg/m2 (OR 3.46, p = 0.006)], a relative decrease in serum albumin after 3 months of treatment increased risk of developing edema (OR 2.07, p = 0.062). Neither duration nor type of therapy were significant risk factors for edema. CONCLUSION: PI3K/mTOR/CDK4/6 inhibitors may influence the development of edema, which may cause or exacerbate progression of BCRL in patients with MBC. The varied incidence of edema between therapeutic regimens warrants vigilant monitoring of patients treated with these therapies, especially those at high risk of developing BCRL.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Linfedema/epidemiologia , Terapia de Alvo Molecular/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/metabolismo , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Feminino , Humanos , Incidência , Linfedema/induzido quimicamente , Pessoa de Meia-Idade , Inibidores de Fosfoinositídeo-3 Quinase , Serina-Treonina Quinases TOR/antagonistas & inibidores
4.
Breast Cancer Res Treat ; 174(1): 179-185, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30478787

RESUMO

PURPOSE: Patients with Her2-positive breast cancer treated with trastuzumab have higher rates of cardiotoxicity (CT). Left-breast radiation might increase the risk for CT from cardiac exposure to radiation. The goal of our study is to evaluate the contribution of radiotherapy (RT) in the development of CT in breast cancer patients receiving trastuzumab. METHODS: Two hundred and two patients were treated with RT and trastuzumab from 2000 to 2014. The RT plans for left-side disease were recalled from archives. The heart, each chamber, and left anterior descending artery (LAD) were independently contoured. New dose-volume histograms (DVH) were generated. Their serial left-ventricular ejection fractions (LVEF) were studied. CT for left and right side were compared using Fisher's exact test. The DVH data were correlated with the predefined cardiac events using actuarial Cox regression analysis. RESULTS: Compared to the right sided, the left-side cases showed statistically significant development of arrhythmia (14.2%) versus (< 1%) (p < 0.001). Cardiac ischemia was found in 10 patients in left and one patient in right side (p = 0.011). The equivalent uniform dose (EUD) to the left ventricle (LV), right ventricle (RV), and LAD was significantly associated with decrease in LVEF by > 10% (p = 0.037, p = 0.023 and p = 0.049, respectively). CONCLUSIONS: Among patients treated for left-sided lesions, there were no significant differences in EF decline. However, there was a higher rate of ischemia and arrhythmia compared to those with right-sided disease. The EUD index of LV, RV, and LAD could be considered as a parameter to describe the risk of radiation-induced CT.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Cardiotoxicidade/etiologia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Cardiotoxicidade/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Órgãos em Risco , Radioterapia/efeitos adversos , Trastuzumab/efeitos adversos
5.
Int J Radiat Oncol Biol Phys ; 103(1): 62-70, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30165125

RESUMO

PURPOSE: The purpose of the study was to determine when the risk of lymphedema is highest after treatment of breast cancer and which factors influence the time course of lymphedema development. METHODS AND MATERIALS: Between 2005 and 2017, 2171 women (with 2266 at-risk arms) who received surgery for unilateral or bilateral breast cancer at our institution were enrolled. Perometry was used to objectively assess limb volume preoperatively, and lymphedema was defined as a ≥10% relative arm-volume increase arising >3 months postoperatively. Multivariable regression was used to uncover risk factors associated with lymphedema, the Cox proportional hazards model was used to calculate lymphedema incidence, and the semiannual hazard rate of lymphedema was calculated. RESULTS: With a median follow-up of 4 years, the overall estimated 5-year cumulative incidence of lymphedema was 13.7%. Significant factors associated with lymphedema on multivariable analysis were high preoperative body mass index, axillary lymph node dissection (ALND), and regional lymph node radiation (RLNR). Patients receiving ALND with RLNR experienced the highest 5-year rate of lymphedema (31.2%), followed by those receiving ALND without RLNR (24.6%) and sentinel lymph node biopsy with RLNR (12.2%). Overall, the risk of lymphedema peaked between 12 and 30 months postoperatively; however, the time course varied as a function of therapy received. Early-onset lymphedema (<12 months postoperatively) was associated with ALND (HR [hazard ratio], 4.75; P < .0001) but not with RLNR (HR, 1.21; P = .55). In contrast, late-onset lymphedema (>12 months postoperatively) was associated with RLNR (HR, 3.86; P = .0001) and, to a lesser extent, ALND (HR, 1.86; P = .029). The lymphedema risk peaked between 6 and 12 months in the ALND-without-RLNR group, between 18 and 24 months in the ALND-with-RLNR group, and between 36 and 48 months in the group receiving sentinel lymph node biopsy with RLNR. CONCLUSIONS: The time course for lymphedema development depends on the breast cancer treatment received. ALND is associated with early-onset lymphedema, and RLNR is associated with late-onset lymphedema. These results can influence clinical practice to guide lymphedema surveillance strategies and patient education.


Assuntos
Neoplasias da Mama/terapia , Linfedema/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Humanos , Incidência , Excisão de Linfonodo , Irradiação Linfática , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Biópsia de Linfonodo Sentinela , Fatores de Tempo , Adulto Jovem
6.
Gland Surg ; 7(4): 379-403, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30175055

RESUMO

Breast cancer-related lymphedema (BCRL) is a negative sequela of breast cancer treatment, and well-established risk factors include axillary lymph node dissection (ALND) and regional lymph node radiation (RLNR). BCRL affects approximately 1 in 5 patients treated for breast cancer, and it has a significant negative impact on patients' quality of life after breast cancer treatment, serving as a reminder of previous illness. This paper is a comprehensive review of the current evidence regarding BCRL risk factors, precautionary guidelines, prospective screening, early intervention, and surgical and non-surgical treatment techniques. Through establishing evidence-based BCRL risk factors, researchers and clinicians are better able to prevent, anticipate, and provide early intervention for BCRL. Clinicians can identify patients at high risk and utilize prospective screening programs, which incorporate objective measurements, patient reported outcome measures (PROM), and clinical examination, thereby creating opportunities for early intervention and, accordingly, improving BCRL prognosis. Innovative surgical techniques that minimize and/or prophylactically correct lymphatic disruption, such as axillary reverse mapping (ARM) and lymphatic-venous anastomoses (LVAs), are promising avenues for reducing BCRL incidence. Nonetheless, for those patients with BCRL who remain unresponsive to conservative methods like complete decongestive therapy (CDT), surgical treatment options aiming to reduce limb volume or restore lymphatic flow may prove to be palliative or corrective. It is only through a strong team-based approach that such a continuum of care can exist, and a multidisciplinary approach to BCRL screening, intervention, and research is therefore strongly encouraged.

7.
Breast Cancer Res Treat ; 172(1): 83-91, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30062571

RESUMO

PURPOSE: Despite increasing emphasis on screening and early intervention for breast cancer-related lymphedema (BCRL), there is marked heterogeneity in diagnostic methodology, including for volumetric measures. This retrospective study compared two volumetric modalities, perometry and simulated circumferential tape measurement (anatomic- and interval-based), for BCRL detection. METHODS: Between 2005 and 2017, 287 female patients with unilateral breast cancer were prospectively screened for BCRL by perometry and the relative volume change (RVC) formula. Circumferential measurement was performed by sampling at five anatomic landmark-based points or 4-cm intervals from pairs of perometer arm diameter measurements. Volumetric conversion was by a frustum model. The Bland-Altman method was used to compare segmental volume differences. Confusion matrix analysis was performed for each circumferential measurement technique against perometry. RESULTS: Median follow-up was 34.7 months over 4 postoperative visits. There was no difference in total arm volume comparing any of the circumferential measurement techniques to perometry. Landmark-based methods significantly underestimated upper arm volume (mean difference - 207 mL [- 336, - 78 mL]) and overestimated forearm volume (mean difference + 170 mL [+ 105, + 237 mL]). Landmark-based methods had greater sensitivity and specificity compared to 4-cm interval methods for detection of both RVC ≥ 10 and 5-10%. Landmark-based methods were comparable to perometry for detection of RVC ≥ 10%, but sensitivity was only 63.2-66.7% for RVC 5-10%. CONCLUSIONS: This hypothesis-generating study suggested the superiority of anatomic landmark-based circumferential tape measurement compared to interval-based methods, while generating questions about the underestimation of upper arm volume and overestimation of forearm volume of circumferential tape measurement compared to perometry.


Assuntos
Antropometria , Linfedema Relacionado a Câncer de Mama/diagnóstico , Neoplasias da Mama/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Braço/fisiopatologia , Linfedema Relacionado a Câncer de Mama/etiologia , Linfedema Relacionado a Câncer de Mama/fisiopatologia , Neoplasias da Mama/complicações , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
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