Experience with reduction mammaplasty combined with breast conservation therapy in the treatment of breast cancer

As the inclusion criteria for breast conservation therapy have continued to evolve to include lower quadrant tumors, very large breasts, and central tumors, the potential for significant disfigurement after breast conservation therapy has also increased. This has led some centers to develop coordinated oncology-plastic surgery approaches to ensure both adequate cancer resection and aesthetic appearance to the breasts. The authors applied this principle to a specific group of breast cancer patients--women with macromastia--who would benefit from reduction mammaplasty. Eleven women were identified from the senior author's (S.L.S.) reconstructive practice who underwent breast conservation therapy followed by breast reconfiguration and bilateral reduction mammaplasty. Preoperative brassiere sizes ranged from 34D to 46D. All women had immediate reduction after frozen sections from the lumpectomy/partial mastectomy margins were determined to be negative. A total of 22 reduction mammaplasties were performed (eight free-nipple grafts, five inferior pedicle flaps, seven superomedial pedicle flaps, and two superolateral flaps) and an average of 1085 g was removed per breast. All patients underwent radiation therapy postoperatively. There were eight minor complications in six patients (one hematoma, one keloid, one radiation burn, two cases of nipple hypopigmentation, and three cases of fat necrosis). After an average of 24 months' follow-up, there were no local recurrences and one death from distant metastasis. Seven of the 11 patients were available and agreed to rate their aesthetic satisfaction on the basis of a scale from 1 to 4, with 4 being the best. The mean satisfaction score was 3.3. Aesthetic outcomes before radiation therapy and after radiation therapy were evaluated by a panel of plastic surgery residents blinded to the purpose of the study. Using a scale of 1 to 4, the aesthetic mean before radiation therapy was 2.9 and the aesthetic mean after radiation therapy was 3.03. By combining breast conservation therapy with breast reconfiguration or reduction in large-breasted women, multiple benefits are derived. Larger segmental or partial mastectomies can be performed without disfigurement risk, ensuring adequate surgical margins. Immediate reconfiguration of the breast with reduction of the contralateral side creates symmetric, aesthetically pleasing breasts; allows contralateral breast tissue to be evaluated; and spares women from undergoing a second operative procedure. Such a coordinated program gives women an important boost, both physically and psychologically, during management of their breast cancer.     

Treatment outcomes and late toxicities of intensity-modulated radiation therapy for 1091 Japanese patients with localized prostate cancer

Aim

This study aimed to evaluate the treatment result of intensity-modulated radiation therapy (IMRT) in a large number of Japanese patients with prostate cancer.

Selecting treatment for high-risk, localized prostate cancer: the case for radiation therapy

Prostate cancers that clinically appear to be localized may nonetheless respond poorly to curative treatment. Pretreatment prostate-specific antigen (PSA) level, biopsy Gleason score, and percentage of positive biopsies are all at least as important as clinical stage in predicting treatment outcome. A patient with a nonpalpable tumor, stage T1c disease, serum PSA of 12 ng/mL, and a Gleason score of 8 to 10 in 2 of 12 biopsy cores has a relatively poor prognosis. In a high-risk patient such as this one, the recommended treatment strategy involves a combination of brachytherapy and conformal external beam radiotherapy. In studies comparing treatments in patients stratified according to a variety of risk measures, this combination has shown biochemical disease-free survival rates superior to those seen following radical prostatectomy. The role of androgen suppression remains unclear.     

Temporal trends in the surgical outcomes of patients with breast cancer

ABSTRACT: BACKGROUND: The incidence of breast cancer has been increasing in Japan over the past three decades, and it is the currently the most common malignancy in Japan. This study investigated the temporal trends of the surgical outcomes in patients with breast cancer. METHODS: We evaluated 543 consecutive patients who underwent breast-cancer resection between 1980 and 2009. The temporal trends in the surgical outcome and clinicopathological features were evaluated separately for the periods covering 1980 to 1989, 1990 to 1999, and 2000 to 2009. RESULTS: The number of patients who underwent resection during these three respective periods were 133, 176, and 234, respectively. All patients were women. The percentage of patients at stages 0 or 1 was 63.2%, 58.5%, and 43.6%, respectively, during the three periods. The mean diameter of tumors in each period was 38, 29, and 30 mm, respectively. The percentage of tumors with positive ER expression was 62.5%, 64.3%, and 69.7%, respectively. In terms of surgical procedures, the use of Halsted's radical mastectomy decreased during each period: from 40.6% of cases to 8.5% and then to 0.4%, while the proportion of breast-conserving therapies increased, from 0% to 12.5%, and finally to 35.9%. The postoperative 10-year survival rates during the three periods were 75.9%, 83.5%, and 84.9%, respectively. The 10-year survival rates of patients with stage II disease during the three periods were 66.2%, 75.7%, and 90.7%, respectively. The prognosis of stage III disease in the three periods also showed a tendency toward improvement, increasing from 37.8% to 64.2%, and finally to 84.5%. CONCLUSION: The survival of patients with stage II and III disease has improved during the past 30 years. Along with the recent advances in drug therapy, the surgical treatment has become less invasive, often because of drug therapy-related modifications.     

Micronuclei in lymphocytes of prostate cancer patients undergoing radiation therapy

To further verify the applicability of the micronucleus (MN) assay in biodosimetry, we measured the MN yield in cytokinesis-blocked (CB) peripheral blood lymphocytes (PBL) of eight prostate cancer (PC) patients. These patients had no previous chemotherapy or radiotherapy (xRT). They were treated with standardized schemes of fractionated pelvic xRT. Before xRT, and at one random time-point during the course of xRT, blood samples were collected from each patient for the following purposes: (1) to verify the relationship between the MN yield in PBL and the estimated equivalent (EQ) total-body absorbed dose; and (2) to evaluate the individual differences of ex vivo radiation dose-response (1-4 Gy) relationship of MN yield in PBL before xRT. The number of xRT fractions, cumulative tumor dose, and EQ total-body absorbed doses of these patients represented a wide range. We found in PBL of these patients that (1) MN yield (Y) increased linearly with the estimated EQ total-body absorbed dose as Y=14.6+9.2D (R(2)=0.7, p=0.007); the distributions of MN yield were overdispersed; the ratio of relative increment of MN yield per 1000 binucleated (BN) PBL ranged from 0.9 to 8.2 (median: 4.1) folds above that of the respective baseline levels; and (2) before xRT, the MN yields also increased linearly with the ex vivo radiation dose; at each radiation dose level, the distributions of MN yield were overdispersed in most patients. In two of the three patients with xRT-induced early side effects (cystitis, diarrhea), the MN yield in PBL induced by ex vivo irradiation before xRT was significantly higher than in the other patients without xRT-induced side effects. These findings suggest that MN yields in CB PBL can be used as an in vivo biodosimeter. Since the differences in individual ex vivo radiation dose-response relationship of MN yield in PBL before xRT appeared to be significant, our preliminary results also suggest that it may be possible to identify individual intrinsic radiosensitivity before the start of xRT.     

Influence of ABCB1 genetic variants in breast cancer treatment outcomes

BackgroundTransportation of anticancer drugs such as anthracyclines across the membrane is regulated by P-glycoprotein encoded by the human multidrug resistance gene 1 (ABCB1). Polymorphisms in the ABCB1 gene (1236C > T, 2677G > T/A, 3435C > T) have been found to be associated with intrinsic and acquired cross resistance to these anticancer drugs. Therefore, the aim of this study is to evaluate the influence of ABCB1 gene polymorphisms in breast cancer treatment outcomes in terms of response and toxicity.MethodResponse to neo-adjuvant chemotherapy was evaluated in 100 patients while grade 2–4 toxicity was followed in 207 patients, who had undergone FEC/FAC chemotherapy. Genotyping for ABCB1 polymorphisms was done by PCR-RFLP. Chi square and logistic regression analyses were used to calculate Odd's ratio using SPSS ver 17.0. A meta analysis was also performed using Comprehensive Meta Analysis Ver 2.ResultsIn response evaluation, 1236C > T polymorphism was significantly associated with treatment response for CT genotype [OR = 5.17(1.3–20.2), P = 0.018] and in dominant model (CC vs CT + TT) [OR = 4.63(1.25–17.0), P = 0.021]. In the toxicity group, the T allele of 1236C>T was associated with grade 2–4 tocxicity [OR 1.48(1.00–2.20), P = 0.049] and the association was also significant in the recessive model [OR 1.88(1.05–3.39), P = 0.033]. For other two SNPs 2677G>T/A and 3435C>T no association was seen with either treatment response or grade 2–4 toxicity. In meta analysis, no overall association was found.ConclusionIn our study, significant association was seen for ABCB1 1236C>T polymorphism with treatment response. The meta analysis did not show overall association with treatment outcomes.     

Prolactin and endocrine therapy resistance in breast cancer: The next potential hope for breast cancer treatment

Breast cancer, a hormone-dependent tumour, generally includes four molecular subtypes (luminal A, luminal B, HER2 enriched and triple-negative) based on oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2. Multiple hormones in the body regulate the development of breast cancer. Endocrine therapy is one of the primary treatments for hormone-receptor-positive breast cancer, but endocrine resistance is the primary clinical cause of treatment failure. Prolactin (PRL) is a protein hormone secreted by the pituitary gland, mainly promoting mammary gland growth, stimulating and maintaining lactation. Previous studies suggest that high PRL levels can increase the risk of invasive breast cancer in women. The expression levels of PRL and PRLR in breast cancer cells and breast cancer tissues are elevated in most ER⁺ and ER⁻ tumours. PRL activates downstream signalling pathways and affects endocrine therapy resistance by combining with prolactin receptor (PRLR). In this review, we illustrated and summarized the correlations between endocrine therapy resistance in breast cancer and PRL, as well as the pathophysiological mechanisms and clinical practices. The study on PRL and its receptor would help explore reversing endocrine therapy-resistance for breast cancer.     

Target therapy in HER2-overexpressing breast cancer patients

The development of new therapeutic strategies, such as monoclonal antibodies directed against human epidermal growth factor receptor-2 (HER2), has offered new hopes for women with early breast cancer whose tumors overexpress HER2. We retrospectively analyzed the population-based data of Breast Cancer Registry of Palermo in 2004-2006, and selected 1401 invasive breast cancer cases, nonmetastatic at diagnosis, having HER2/neu oncogene expression determined. We have correlated this information to age, tumor stage at diagnosis (TNM), nodal involvement, and receptor status (ER and PgR). Survival analysis was conducted dividing the patients in two different groups according to date of diagnosis: one group diagnosed in 2004 and a second group in 2005-2006. In the 460 cases of 2004, nodal involvement, receptor status, age at diagnosis and TNM maintained a strong predictive value (p?相似文献   

Psychological support for patients undergoing breast cancer surgery: a randomised study.

OBJECTIVE--To evaluate the effect of support from a nurse specialising in breast care and a voluntary support organisation on prevalence of psychological morbidity after surgery for breast cancer. DESIGN-- Prospective randomised study. SETTING--Three teaching hospitals in Glasgow with established breast clinics. SUBJECTS--272 women aged less than 70 years undergoing surgery for breast cancer. INTERVENTIONS-- Patients were randomly allocated to receive routine care from ward staff, routine care plus support from breast care nurse, routine care plus support from voluntary organisation, or routine care plus support from nurse and organisation. MAIN OUTCOME MEASURES--Prevalence of psychological morbidity as assessed by self rating scales: 28 item general health questionnaire and its subscales, and hospital anxiety and depression scale. Measurements were made at first postoperative clinic visit and at three, six, and 12 months after surgery. RESULTS-- On each self rating scale, psychological morbidity tended to fall over the 12 month period. For each scale, scores were consistently lower in patients offered support from breast care nurse alone compared with the other groups, which were similar to each other. Differences were significant or nearly so: P values were 0.015 (28 item general health questionnaire), 0.027 (anxiety and insomnia), 0.072 (severe depression), 0.053 (somatic symptoms), 0.031 (social dysfunction), 0.093 (hospital anxiety), and 0.003 (hospital depression). CONCLUSION-- Support from breast care nurse can significantly reduce psychological morbidity, as measured by self rating scales, in women undergoing breast cancer surgery.     

Perspectives for the hormonal therapy of breast cancer

The role of estrogens, including its sources, tissue distribution, metabolism, and mechanism of action, is discussed in this review. The ER alpha and beta are functioning separately, and there is a physiological balance between their activity. Whenever this balance is over thrown due to endogenous or exogenous carcinogenic factors, malignancy develops. Risk factors of breast cancer are listed and evaluated individually. It should be stressed however, that their carcinogenic effect sums up. The knowledge of established risk factors rises the possibility of chemoprevention, which might be highly desirable in case of gene carriers. Special emphasis is attached to the SERM molecules which act as antiestrogens. Their antitumour effect is largely used in the treatment of hormone sensitive advanced breast cancer patients, and their efficacy has been proved in adjuvant therapy as well. Their preventive use might also be justified, especially in gene carriers. Aromatase inhibitors form a special class among the SERM molecules. In Hungary, anastrozole, letrozole and exemestane are widely applied for the therapy of breast cancer patients, while raloxifene has only been introduced recently, mainly in order to prevent osteoporosis. The therapeutic value of fulvestrant is unknown yet and its antitumour effect has to be explored. The therapeutic significance of these molecules lies in the fact that they might be effective after the development of tamoxifen resistance. There are several explanations for this phenomenon offering new targets for the further development of a succesful antitumour chemotherapy.     

Nitroblue tetrazolium test in patients with breast cancer undergoing mastectomy and radiotherapy

The reduction of nitrotetrazolium blue with stimulated and unstimulated granulocytes was performed in 40 patients with breast cancer. Blood was collected from peripheral vein before surgical intervention, during surgery from vein draining of tumor, two weeks after surgery and three months after surgery when radiotherapy was finished. In parallel experiments the NBT test was made in the peripheral blood of 20 healthy individuals. We have observed decreased reduction of nitrotetrazolium blue in stimulated granulocytes, which may indicate that granulocytes from these patients are unable for efficient stimulation. No evident effect concerning the advancement of disease and applied therapy could be found. The importance of determining the NBT test in cancer patients is briefly discussed.     

Finding of no tumor (pT0) in patients undergoing radical retropubic prostatectomy for clinically localized prostate cancer

OBJECTIVE: To evaluate features and clinical outcome of patients with clinically localized prostate cancer graded pT0 following radical retropubic prostatectomy (RRP). STUDY DESIGN: Between 1974 and 2001 we performed 1,135 RRPs for cT1-T2 prostate cancer, of which 386 (34%) underwent 3-6 months of neoadjuvant endocrine treatment (NHT) before RRP. Median clinical follow-up was 53.8 months (range 24-251). Estimation of likelihood events for biochemical relapse was calculated according to the Kaplan-Meier method. Statistical differences between curves were calculated using the log-rank test. RESULTS: In 24 cases (2.12%) routine histologic workup failed to detect residual tumor. The pT0 group contained a higher proportion of cTla-b patients and a biopsy Gleason score < or =6. A tendency toward lower pre-operatory PSA levels in the pT0 group compared to the pT2-3 group was shown. PSA progression was observed in 3 pT0 patients, all of whom previously underwent NHT. CONCLUSION: Patients pT0 at RRP presented with lower preoperative PSA values and low preoperative Gleason score compared to the pT+ group. Absence of tumor at pathology examination has a different clinical meaning when it occurs following NHT or in untreated patients. Patients pT0 after NHT may have a worse clinical outcome than pT0 untreated patients.     

4-Hydroxyandrostenedione treatment for postmenopausal patients with advanced breast cancer

We have treated 128 postmenopausal women with advanced breast cancer with 4-hydroxyandrostenedione. Of these, 118 were assessable for toxicity and 100 for response to treatment. Response to therapy was seen in 34% of patients and stabilization of disease in 12 patients. Three dose regimens were used (500 mg intramuscularly weekly; 250 mg intramuscularly every 2 weeks; and 500 mg orally daily). There was no difference in response in these three groups. Side effects were minimal and local reaction to injected drug was seen in 13% of patients. The sole severe side effect observed was neutropenia which was transient and reversible on discontinuing therapy. 4-Hydroxyandrostenedione is an effective nontoxic agent in the treatment of breast cancer.