Atypical hyperplasia and breast cancer risk: a critique

The purpose of this paper is to examine critically the evidence that atypical hyperplasia (AH) is a risk factor for breast cancer. First, we appraised studies that have examined the association between AH and breast cancer risk for their adherence to widely accepted standards for the conduct of research. Second, we examined the a vailable evidence to determine the plausibility of an association between AH and breast cancer risk using the guidelines proposed by Bradford Hill. A total of 18 studies (11 cohort studies, two case-control studies, and five cross-sectional studies) were found that were published in the English language from January 1960 to March 1992 that examined the association of AH as a distinct entity and breast cancer risk. A systematic approach was adopted to examine the collected studies for their adherence to methodologic standards, which showed wide variation among studies. A meta-analysis was carried out, based on a total sample size of 182,980 women. Of 16 studies that gave point estimates of risk, 14 exceeded unity and 12 were significantly different from unity. The pooled estimate from all studies of the association between AH and breast cancer, gave an overall odds ratio (OR) of 3.67 (95 percent confidence interval = 3.16–4.26). The test of the hypothesis of homogeneous association was rejected (² = 151.6, df = 14, P<0.0001), indicating significant variability among the ORs of individual studies. The conclusions from the application of the Bradford Hill criteria indicated strongly that AH is a risk factor for breast cancer.     

Immediate breast reconstruction following modified radical mastectomy

Reducing postoperative psychological morbidity is an important goal in breast cancer patient care; a multidisciplinary approach is crucial in order to select candidates for immediate breast reconstruction. There is no oncologic reason for a delay after a modified radical mastectomy. Our procedure allows immediate breast reconstruction without significantly prolonging operative time and hospitalization. Complete muscular coverage of the implant and shifting of the redundant skin to the mastectomy site minimize the risk of postoperative complications and provide a natural looking reconstructed breast. Delayed reconstruction of the nipple-areolar complex performed at the time of contralateral mammaplasty ensures satisfactory breast symmetry. Satisfactory reconstruction of the nipple-areolar complex is achieved without additional scars by means of grafts taken from the opposite breast or utilizing the cryopreserved nipple and areola.     

Radiotherapy and breast reconstruction: a meta-analysis

The optimum sequencing of breast reconstruction (BR) in patients receiving postmastectomy radiation therapy (PMRT) is controversial. A comprehensive search of published studies that examined postoperative morbidity following immediate or delayed BR with combined radiotherapy was performed. Medical (MEDLINE & EMBASE) databases were searched and cross-referenced for appropriate studies where morbidity following BR was the primary outcome measured. A total of 1,105 patients were identified from 11 appropriately selected studies. Patients undergoing PMRT and BR are more likely to suffer morbidity compared with patients not receiving PMRT (OR = 4.2; 95% CI, 2.4–7.2 [no PMRT vs. PMRT]). Reconstruction technique was also examined with outcome when PMRT was delivered after BR, and this demonstrated that autologous reconstruction is associated with less morbidity in this setting (OR = 0.21; 95% CI, 0.1–0.4 [autologous vs. implant-based]). Delaying BR until after PMRT had no significant effect on outcome (OR = 0.87; 95% CI, 0.47–1.62 [delayed vs. immediate]). PMRT has a detrimental effect on BR outcome. These results suggest that where immediate reconstruction is undertaken with the necessity of PMRT, an autologous flap results in less morbidity when compared with implant-based reconstruction.     

Chronic pain following treatment for cancer: the role of opioids

Opioids are the most effective analgesics for severe pain and the mainstay of acute and terminal cancer pain treatments. In those settings, opioids are used over a limited time period so that opioid tolerance, if it develops, is relatively easy to overcome, and other problems of opioid use, including substance abuse, are unlikely to be problematic. As cancer treatments improve and increasing numbers of cancer patients experience long remissions, chronic pain due to cancer, or to cancer treatment, becomes a clinical problem that oncologists will encounter. Chronic pain differs from acute and terminal pain in several fundamental respects. In the case of chronic pain, functional restoration is a predominant goal of treatment. Because it is often due to neuronal damage, the pain may be particularly sensitive to nonopioid medications, and opioids can be reserved for refractory pain. If opioids are chosen, tolerance, dependence, and addiction can interfere, and safeguards designed to minimize these must be built into the treatment plan. This article reviews the principles of chronic opioid therapy for non-cancer pain and how these principles may be adapted for patients with chronic pain due to cancer.     

Sexual dysfunction following tram flap breast reconstruction for breast cancer: A preliminary communication

Psychological and social problems have been documented as sequelae of mastectomy. Patients may experience depression, anxiety, decreased sexual interest, negative changes in body image, fears of recurrence and concerns regarding the mastectomy site or prosthesis. Immediate breast reconstruction, using improved techniques such as the TRAM flap, have lessened the negative psychological impact of mastectomy but whether these procedures themselves result in psychologic or sexual impairment has not been reported. We, therefore, report four patients, three of whom were self-referred for psychiatric evaluation, who experienced changes in body image and sexual response after TRAM flap reconstruction. Although the TRAM flap procedure cannot be specifically implicated, the similar presentation and complaints in these four cases suggest a possible association that warrants more rigorous study.     

Pedicled dermoglandular flap reconstruction following breast conserving surgery

Breast conserving therapy is the gold standard treatment of early breast cancer. However, a balance between good cosmetic outcome and limiting the risk of locoregional recurrence remains the key of success.The aim of this work was to evaluate the outcome of partial breast reconstruction using pedicled dermo-glandular flap from the upper outer quadrant, for central quadrantectomy BCS.Patients & methodsThirty patients underwent wide excision of carcinoma of retroareolar or periareolar regions of the breast, from July 2008 to August 2011. Excisions included the nipple/areola complex down to the pectoralis fascia with a wide safety margin, and complete axillary dissection. Breast reconstruction was done by means of pedicled dermoglandular flap.ResultsMean age of patients was 51.86 years (range from 30 to 70 years). Tumor size ranged from 1 to 4.2 cm. Postoperative pathological results came out with 21 (70.0%) patients mean (range) of the tumor safety margin 2.01 (0.5–2.8). Seventeen (56.7%) patients had positive axillary lymph nodes. All patients received postoperative radiation therapy to the breast, while 17/30 (56.67%) and 6/30 (20%) received endocrine therapy or adjuvant chemotherapy, respectively, and only 7/30 (23.34%) patients received both therapies. During a median follow-up period of 24 months, neither local nor distant metastasis, were detected. The postoperative cosmetic result was excellent in 80% patients, good in 13.3% patients, acceptable in 6.7% with no poor result.ConclusionFollowing central quadrantectomy BCS for small centrally located breast cancer, a pedicled dermoglandular flap from the upper outer quadrant is a good reconstructive option.     

Options for immediate breast reconstruction following skin-sparing mastectomy

Background  Skin-sparing mastectomy (SSM) is a type of breast cancer surgery presupposed as breast reconstruction surgery. Cosmetically, it is an extremely effective breast cancer operation because the greater part of the breast’s native skin and infra-mammary fold are conserved. All cases of SSM and immediate breast reconstruction performed by the senior author during the last five years were reviewed. as]Methods: There are three implant options for breast reconstruction, namely, deep inferior epigastric perforator (DIEP) flap, latissimus dorsi myocutaneous (LDM) flap, and breast implant, and one of these was used for reconstruction after comprehensive evaluation. Results  From 2001 to 2005, immediate reconstructions following SSM were performed on 124 cases (128 breasts) by the same surgeon. Partial necrosis of the breast skin occurred in 4 cases of SSM. The mean follow-up was 33.6 months. During the follow-up, there was local recurrence following surgery in 3 cases. The overall aesthetic results of immediate breast reconstruction after SSM are better than those after non-SSM. Conclusion  SSM preserves the native breast skin and infra-mammary fold, and is an extremely useful breast cancer surgery for breast reconstruction. SSM is an excellent breast cancer surgical technique. We think this procedure should be considered in more facilities conducting breast reconstruction in Japan.     

乳腺癌术后乳房重建的研究现状及其评价

目前，中国乳腺癌的发病率呈现不断上升趋势。据统计，北京、上海、广州、天津等大城市每年新发乳腺癌患者占总女性人口的50／10万～60／10万，位居第一。随着学者们对乳腺癌认识的不断提高，乳腺癌的早期发现率也明显提高，加之治疗手段的完善和辅助治疗方法的应用，乳腺癌患者的生存率已大大提高，其对手术后的生活质量也有了更高的要求嵋。     

Options for immediate breast reconstruction following skin-sparing mastectomy.

BACKGROUND: Skin-sparing mastectomy (SSM) is a type of breast cancer surgery presupposed as breast reconstruction surgery. Cosmetically, it is an extremely effective breast cancer operation because the greater part of the breast's native skin and infra-mammary fold are conserved. All cases of SSM and immediate breast reconstruction performed by the senior author during the last five years were reviewed. METHODS: There are three implant options for breast reconstruction, namely, deep inferior epigastric perforator (DIEP) flap, latissimus dorsi myocutaneous (LDM) flap, and breast implant, and one of these was used for reconstruction after comprehensive evaluation. RESULTS: From 2001 to 2005, immediate reconstructions following SSM were performed on 124 cases (128 breasts) by the same surgeon. Partial necrosis of the breast skin occurred in 4 cases of SSM. The mean follow-up was 33.6 months. During the follow-up, there was local recurrence following surgery in 3 cases. The overall aesthetic results of immediate breast reconstruction after SSM are better than those after non-SSM. CONCLUSION: SSM preserves the native breast skin and infra-mammary fold, and is an extremely useful breast cancer surgery for breast reconstruction. SSM is an excellent breast cancer surgical technique. We think this procedure should be considered in more facilities conducting breast reconstruction in Japan.     

Locoregional recurrence following nipple-sparing mastectomy with immediate breast reconstruction: Patterns and prognostic significance

IntroductionThere are limited available data on the prognostic implications of locoregional recurrence (LRR) after nipple-sparing mastectomy (NSM) and immediate reconstruction. In this study, we investigated the patterns and prognosis associated with LRR following this treatment approach for breast cancer.MethodsA total of 1696 patients with primary breast cancer who underwent NSM with immediate reconstruction from March 2003 to December 2016 were retrospectively analyzed. Post-recurrence disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses using the Cox proportional hazards model were performed to evaluate the prognostic factors associated with the DFS and DMFS.ResultsAfter a median follow-up period of 84 months, we identified 172 patients (10.1%) with an LRR as the first event. The 5-year post-recurrence DFS rates for the nipple-areola complex recurrence (NCR), skin or subcutaneous recurrence/chest wall recurrence (SCR/CWR), and regional recurrence (RR) groups were 89.1%, 73%, and 59.4%, respectively (P = 0.009), and the 5-year post-recurrence DMFS rates for the NCR, SCR/CWR, and RR groups were 96%, 82.8%, and 59.7%, respectively (P < 0.001). In multivariate analysis, a time to LRR ≤2 years (P = 0.016) and the site of LRR (P = 0.022) were significantly associated with the post-recurrence DFS.ConclusionsNCR is more likely to be detected as a non-invasive recurrence and is associated with more favorable overall outcomes than other LRR types. The interval to LRR and its site of onset seem to be associated with the prognostic outcomes.     

Dietary genistein reduces metastasis in a postsurgical orthotopic breast cancer model

Metastatic spread, not primary tumor burden, is the leading cause of breast cancer deaths. For patient prognosis to improve, new systemic adjuvant therapies that are capable of effectively inhibiting the outgrowth of seeded tumor cells after surgical treatment of the primary breast tumor are needed. To facilitate the preclinical development of such therapies, relevant animal models of breast cancer metastasis that can mimic the postsurgical adjuvant setting are required. Here we developed a preclinical xenograft model of breast cancer metastasis where the primary tumor was removed by surgical resection before systemic adjuvant treatment. We used this model to assess the antimetastatic effect of postsurgical dietary intervention with the soy isoflavone genistein. The anticancer activity of genistein has been established in vitro and in vivo, however, few studies have tested the potential of genistein as an antimetastatic therapy. Using our model, we tested the efficacy of adjuvant treatment with genistein to inhibit the outgrowth of metastases postsurgery. To establish primary tumors, human breast carcinoma cells, MDA-MB-435/HAL, were implanted into the mammary fat pad of female nude mice. Primary tumors were left to grow for 5 weeks before being surgically removed. Mice were then randomized into two diet groups: control soy-free diet versus genistein-supplemented diet. Five weeks later, metastatic burden was assessed. Genistein reduced the percent metastatic burden in the lungs by 10-fold. These results indicate that dietary intervention following cancer surgery can affect the outgrowth of seeded tumor cells. The availability of well-characterized, clinically relevant animal models for studying factors that regulate metastatic outgrowth postsurgery will provide an important tool for developing new systemic adjuvant therapies.