Immediate postmastectomy reconstruction

The role of reconstruction in the management of patients with problems related to breast cancer is of increasing importance. Immediate reconstruction is particularly applicable in those situations where prophylactic mastectomy is performed. High-risk groups who warrant such prophylactic mastectomy and reconstruction include those with florid cyst disease, a strong family history of breast cancer, the finding of lobular carcinoma in situ, multiple previous biopsies, and those who have severe and progressive mastodynia. In those with smaller amounts of breast tissue, reconstruction is based on a double layer of tissue over a graft, one layer consisting of pectoral muscle and the other of breast skin. In those with more abundant breast tissue, the two layers placed over the graft are both derived from skin flaps, the inner layer a free, denuded dermal graft from the inferior flap and the second layer, the superior breast skin flap itself.     

Estimating breast cancer‐specific and other‐cause mortality in clinical trial and population‐based cancer registry cohorts

BACKGROUND:

To compute net cancer‐specific survival rates using population data sources (eg, the National Cancer Institute's Surveillance, Epidemiology, and End Results [SEER] Program), 2 approaches primarily are used: relative survival (observed survival adjusted for life expectancy) and cause‐specific survival based on death certificates. The authors of this report evaluated the performance of these estimates relative to a third approach based on detailed clinical follow‐up history.

METHODS:

By using data from Cancer Cooperative Group clinical trials in breast cancer, the authors estimated 1) relative survival, 2) breast cancer‐specific survival (BCSS) determined from death certificates, and 3) BCSS obtained by attributing cause according to clinical events after diagnosis, which, for this analysis was considered the benchmark “true” estimate. Noncancer life expectancy also was compared between trial participants, SEER registry patients, and the general population.

RESULTS:

Among trial patients, relative survival overestimated true BCSS in patients with lymph node‐negative breast cancer; whereas, in patients with lymph node‐positive breast cancer, the 2 estimates were similar. For higher risk patients (younger age, larger tumors), relative survival accurately estimated true BCSS. In lower risk patients, death certificate BCSS was more accurate than relative survival. Noncancer life expectancy was more favorable among trial participants than in the general population and among SEER patients. Tumor size at diagnosis, which is a potential surrogate for screening use, partially accounted for this difference.

CONCLUSIONS:

In the clinical trials, relative survival accurately estimated BCSS in patients who had higher risk disease despite more favorable other‐cause mortality than the population at large. In patients with lower risk disease, the estimate using death certificate information was more accurate. For SEER data and other data sources where detailed postdiagnosis clinical history was unavailable, death certificate‐based estimates of cause‐specific survival may be a superior choice. Cancer 2009. © 2009 American Cancer Society.     

Good clinical response of breast cancers to neoadjuvant chemoendocrine therapy is associated with improved overall survival.

BACKGROUND: We present extended follow-up from a prospective randomised trial evaluating the role of neoadjuvant chemoendocrine therapy in the treatment of operable breast cancer. PATIENTS AND METHODS: 309 women were randomised to primary surgery followed by eight cycles of adjuvant mitoxantrone, methotrexate with tamoxifen (2MT) or 2MT with mitomycin-C (3MT) versus the same regimen for four cycles before followed by four cycles after surgery. For this analysis the median follow-up of patients was 112 months. RESULTS: After 10 years follow-up there is still no statistically significant difference in disease-free survival (DFS) (71% versus 71%) or overall survival (OS) (63% versus 70%) when comparing adjuvant versus neoadjuvant treatment, respectively. Of 144 evaluable patients in the neoadjuvant arm, 74 achieved a good clinical response and 70 patients achieved a poor clinical response. Good responders had a superior DFS (80% versus 64%, P=0.01) and OS (77% versus 63%, P=0.03) compared to poor responders. CONCLUSIONS: At 10 years, neoadjuvant and adjuvant treatment continue to have equivalent OS and DFS. Good clinical response to neoadjuvant chemotherapy is associated with superior DFS and OS. This supports the use of clinical response of primary breast cancer to neoadjuvant therapy as a surrogate marker of survival benefit.     

Assessing the utility of cancer‐registry–processed cause of death in calculating cancer‐specific survival

BACKGROUND:

Cancer registries use algorithms to process cause of death (COD) data from death certificates, but uncertainties remain regarding the accuracy and utility of those data in calculating cancer‐specific survival (CSS). Because it is impractical to reconfirm the COD through meticulous review of the primary medical records, the observed cancer deaths could be compared with the number of attributed deaths, as estimated by using a relative survival (RS) approach, to determine utility in CSS estimation.

METHODS:

Six major cancer types were evaluated using Surveillance, Epidemiology, and End Results (SEER) data (1988‐1999 cohort). The COD utility was quantified by using the observed‐to‐expected ratio (O/E ratio) approach, which was calculated as the SEER‐documented observed number of cancer‐specific deaths divided by the number of expected deaths attributed to the malignancies as estimated using a RS approach. Favorable utility would have an O/E ratio close to 1.

RESULTS:

In total, 338,445 patients were identified; and their O/E ratios were 0.97, 0.98, 0.90, 1.07, 1.02, and 0.92 for breast, colorectal, lung, melanoma, prostate, and pancreas cancer, respectively. O/E ratios varied slightly with patients' age, race, and tumor stage, but not by sex. CSS for patients with lung cancer appeared to be overestimated considerably. Patients with multiple cancer diagnoses had poor O/E ratios compared with those who had only 1 cancer.

CONCLUSIONS:

The utility of COD in calculating CSS depended variously on the risk of cancer‐related mortality and nontumor factors. However, the impact of this variation on CSS generally was small. The current results indicated that the COD assigned by cancer registries has acceptable validity, and CSS is considered an acceptable surrogate for RS in most circumstances. Cancer 2013. © 2013 American Cancer Society.     

PI3K pathway activation in breast cancer is associated with the basal‐like phenotype and cancer‐specific mortality

Breast cancer is a common malignancy with current biological therapies tailored to steroid hormone (ER, PR) and HER2 receptor status. Understanding the biological basis of resistance to current targeted therapies and the identification of new potential therapeutic targets is an ongoing challenge. The PI3K pathway is altered in a high proportion of breast cancers and may contribute to therapeutic resistance. We undertook an integrative study of mutational, copy number and expression analyses of key regulators of the PI3K pathway in a cohort of 292 invasive breast cancer patients with known treatment outcomes. The alterations identified in this cohort included PIK3CA mutations (12/168, i.e. 7%), PIK3CA copy number gain (28/209, i.e. 14%), PTEN loss (73/258, i.e. 28%) and AKT activation (62/258, i.e. 24%). Overall at least 1 parameter was altered in 72% (139/193) of primary breast cancers. PI3K pathway activation was significantly associated with ER negative (p = 0.0008) and PR negative (p = 0.006) status, high tumor grade (p = 0.032) and a “basal‐like” phenotype (p = 0.01), where 92% (25/27) of tumors had an altered pathway. In univariate analysis, PI3K pathway aberrations were associated with death from breast cancer; however, this relationship was not maintained in multivariate analysis. No association was identified between an activated pathway and outcome in tamoxifen‐ or chemotherapy‐treated patients. We concluded that >70% of breast cancers have an alteration in at least 1 component of the PI3K pathway and this might be exploited to therapeutic advantage especially in “basal‐like” cancers.     

The impact of risk‐reducing hysterectomy and bilateral salpingo‐oophorectomy on survival in patients with a history of breast cancer—A population‐based data linkage study

Prophylactic surgery including hysterectomy and bilateral salpingo‐oophorectomy (BSO) is recommended in breast cancer susceptibility gene (BRCA)‐positive women, whereas in women from the general population, hysterectomy plus BSO may increase the risk of overall mortality. The effect of hysterectomy plus BSO on women previously diagnosed with breast cancer is unknown. We used data from a population‐base data linkage study of all women diagnosed with primary breast cancer in Queensland, Australia between 1997 and 2008 (n = 21,067). We fitted flexible parametric breast cancer‐specific and overall survival models with 95% confidence intervals (also known as Royston–Parmar models) to assess the impact of risk‐reducing surgery (removal of uterus, one or both ovaries). We also stratified analyses by age 20–49 and 50–79 years, respectively. Overall, 1,426 women (7%) underwent risk‐reducing surgery (13% of premenopausal women and 3% of postmenopausal women). No women who had risk‐reducing surgery compared to 171 who did not have risk‐reducing surgery developed a gynaecological cancer. Overall, 3,165 (15%) women died, including 2,195 (10%) from breast cancer. Hysterectomy plus BSO was associated with significantly reduced risk of death overall [adjusted hazard ration (HR), 0.69; 95% confidence interval (CI), 0.53–0.89; p = 0.005]. Risk reduction was greater among premenopausal women, whose risk of death halved (HR, 0.45; 95% CI, 0.25–0.79; p < 0.006). This was largely driven by reduction in breast cancer‐specific mortality (HR, 0.43; 95% CI, 0.24–0.79; p < 0.006). This population‐based study found that risk‐reducing surgery halved the mortality risk for premenopausal breast cancer patients. Replication of our results in independent cohorts and subsequently randomised trials are needed to confirm these findings.     

Postdiagnosis weight change is associated with poorer survival in breast cancer survivors: A prospective population‐based patient cohort study

More women are surviving after breast cancer due to early detection and modern treatment strategies. Body weight also influences survival. We aimed to characterize associations between postdiagnosis weight change and prognosis in postmenopausal long‐term breast cancer survivors. We used data from a prospective population‐based patient cohort study (MARIE) conducted in two geographical regions of Germany. Breast cancer patients diagnosed 50 to 74 years of age with an incident invasive breast cancer or in situ tumor were recruited from 2002 to 2005 and followed up until June 2015. Baseline weight was ascertained at an in‐person interview at recruitment and follow‐up weight was ascertained by telephone interview in 2009. Delayed entry Cox proportional hazards regression was used to assess associations between relative weight change and all‐cause mortality, breast cancer mortality, and recurrence‐free survival. In total, 2216 patients were included. Compared to weight maintenance (within 5%), weight loss >10% increased risk of all‐cause mortality (HR 2.50, 95% CI 1.61, 3.88), breast cancer mortality (HR 3.07, 95% CI 1.69, 5.60) and less so of recurrence‐free survival (HR 1.43, 95% CI 0.87, 2.36). Large weight gain of >10% also increased all‐cause mortality (HR 1.64, 95% CI 1.02, 2.62) and breast cancer mortality (HR 2.25, 95% CI 1.25, 4.04). Weight maintenance for up to 5 years in long‐term breast cancer survivors may help improve survival and prognosis. Postdiagnosis fluctuations in body weight of greater than 10% may lead to increased mortality. Survivors should be recommended to avoid large deviations in body weight from diagnosis onwards to maintain health and prolong life.     

组织扩张术在即刻乳房再造中的应用

目的改进即刻乳房再造的手术方法,将软组织扩张术应用于即刻乳房再造术中,避免再造乳房术后出现"补丁样"外观,并保留乳房再造的最佳条件。方法在乳腺癌切除后即刻于胸大肌后间隙置入圆形扩张器,并于术后8~12周注水扩张至理想体积。Ⅱ期再造手术采用硅凝胶乳房假体、背阔肌肌皮瓣+硅凝胶乳房假体、背阔肌肌皮瓣及DIEP皮瓣置换扩张器完成乳房再造。结果 2009年6月至2011年6月,采用该技术进行扩张法即刻乳房再造36例,平均完成乳房再造时间3.5个月。术后无假体外露、皮瓣坏死等并发症出现,也无原手术切口的延长或新手术切口增加。术后随访6~12个月,患者对手术效果满意率达97.2%。结论采用组织扩张法进行即刻乳房再造,可以保留最佳的乳房再造条件,避免了术后放疗对乳房假体的影响,可以避免由于采用皮瓣修补胸部皮肤缺损而出现的"补丁样"外观,是理想的即刻乳房再造方法之一。     

Public health insurance and cancer‐specific mortality risk among patients with breast cancer: A prospective cohort study in China

Little is known about how health insurance policies, particularly in developing countries, influence breast cancer prognosis. Here, we examined the association between individual health insurance and breast cancer‐specific mortality in China. We included 7436 women diagnosed with invasive breast cancer between 2009 and 2016, at West China Hospital, Sichuan University. The health insurance plan of patient was classified as either urban or rural schemes and was also categorized as reimbursement rate (ie, the covered/total charge) below or above the median. Breast cancer‐specific mortality was the primary outcome. Using Cox proportional hazards models, we calculated hazard ratios (HRs) for cancer‐specific mortality, contrasting rates among patients with a rural insurance scheme or low reimbursement rate to that of those with an urban insurance scheme or high reimbursement rate, respectively. During a median follow‐up of 3.1 years, we identified 326 deaths due to breast cancer. Compared to patients covered by urban insurance schemes, patients covered by rural insurance schemes had a 29% increased cancer‐specific mortality (95% CI 0%‐65%) after adjusting for demographics, tumor characteristics and treatment modes. Reimbursement rate below the median was associated with a 42% increased rate of cancer‐specific mortality (95% CI 11%‐82%). Every 10% increase in the reimbursement rate is associated with a 7% (95% CI 2%‐12%) reduction in cancer‐specific mortality risk, particularly in patients covered by rural insurance schemes (26%, 95% CI 9%‐39%). Our findings suggest that underinsured patients face a higher risk of breast cancer‐specific mortality in developing countries.     

Germline mutation in DNA‐repair genes is associated with poor survival in BRCA1/2‐negative breast cancer patients

BRCA1/2 genes are the most frequently germline mutated DNA‐repair genes, and the survival of BRCA1/2 carriers has been extensively explored in breast cancer. However, the prevalence of germline mutations in non‐BRCA1/2 DNA‐repair genes and the survival of carriers are largely unknown in a large cohort of unselected breast cancer patients. Germline mutations in 16 DNA‐repair genes were determined using a multigene panel in 7657 BRCA1/2‐negative breast cancer patients who were unselected for family history of cancer or age at diagnosis. Among the 7657 BRCA1/2‐negative breast cancer patients, 257 (3.4%) carried at least 1 pathogenic germline mutation in the 16 DNA‐repair genes. The prevalence of DNA‐repair gene mutations was significantly higher in familial breast cancers (5.2%, P = 0.002) and early‐onset breast cancers (diagnosed at and before the age of 40) (4.5%, P = 0.003) than that of sporadic breast cancers (2.9%) (diagnosed above age of 40), respectively. The DNA‐repair gene mutation carriers were significantly more likely to have a larger tumor (P = 0.04) and axillary lymph node metastasis (P = 0.03). Moreover, DNA‐repair gene mutation was an independent unfavorable factor for recurrence‐free survival (adjusted hazard ratio [HR] = 1.38, 95% CI: 1.00‐1.91, P = 0.05) and disease‐specific survival (adjusted HR=1.63, 95% CI: 1.04‐2.57, P = 0.03) in this cohort. Overall, 3.4% of BRCA1/2‐negative breast cancer patients carried germline mutations in the 16 DNA‐repair genes, and the DNA‐repair gene mutation carriers exhibited an aggressive phenotype and had poor survival compared with noncarriers.     

Breast conserving therapy and mastectomy revisited: Breast cancer‐specific survival and the influence of prognostic factors in 129,692 patients

This large population‐based study compared breast‐conserving surgery with radiation therapy (BCT) with mastectomy on (long‐term) breast cancer‐specific (BCSS) and overall survival (OS), and investigated the influence of several prognostic factors. Patients with primary T1‐2N0‐2M0 breast cancer, diagnosed between 1999 and 2012, were selected from the Netherlands Cancer Registry. We investigated the 1999–2005 (long‐term outcome) and the 2006–2012 cohort (contemporary adjuvant systemic therapy). Cause of death was derived from the Statistics Netherlands (CBS). Multivariable analyses, per time cohort, were performed in T1‐2N0‐2, and separately in T1‐2N0‐1 and T1‐2N2 stages. The T1‐2N0‐1 stages were further stratified for age, hormonal receptor and HER2 status, adjuvant systemic therapy and comorbidity. In total, 129,692 patients were included. In the 1999–2005 cohort, better BCSS and OS for BCT than mastectomy was seen in all subgroups, except in patients < 40 years with T1‐2N0‐1 stage. In the 2006–2012 cohort, superior BCSS and OS were found for T1‐2N0‐1, but not for T1‐2N2. Subgroup analyses for T1‐2N0‐1 showed superior BCSS and OS for BCT in patients >50 years, not treated with chemotherapy and with comorbidity. Both treatments led to similar BCSS in patients <50 years, without comorbidity and those treated with chemotherapy. Although confounding by severity and residual confounding cannot be excluded, this study showed better long‐term BCSS for BCT than mastectomy. Even with more contemporary diagnostics and therapies we identified several subgroups that may benefit from BCT. Our results support the hypothesis that BCT might be preferred in most breast cancer patients when both treatments are suitable.     

Patient satisfaction with postmastectomy breast reconstruction: a comparison of saline and silicone implants

BACKGROUND.

At a time when the safety and effectiveness of breast implants remains under close scrutiny, it is important to provide reliable and valid evidence regarding patient outcomes. In the setting of postmastectomy reconstruction, patient satisfaction and quality of life may be the most significant outcome variables when evaluating surgical success. The objective of the current study was to identify predictors of patient satisfaction with breast appearance, including implant type, in a large sample of women who underwent breast reconstruction surgery using implants.

METHODS.

A multicenter, cross‐sectional study design was used. A total of 672 women who had completed postmastectomy, implant‐based reconstruction at 1 of 3 centers in North America were asked to complete the BREAST‐Q (Reconstruction Module). Multivariate linear regression modeling was performed.

RESULTS.

Completed questionnaire data were available for 482 of the 672 patients. In 176 women, silicone implants were placed and in 306, saline implants were used. The multivariate model confirmed that patients' satisfaction with their breasts was significantly higher in patients with silicone implants (P = .016). The receipt of postmastectomy radiotherapy was found to have a significant, negative effect on breast satisfaction (P<.000) in both silicone and saline implant recipients. In addition, for women who received either silicone or saline implants, satisfaction diminished over time (P = .017).

CONCLUSIONS.

In the setting of postmastectomy reconstruction, patients who received silicone breast implants reported significantly higher satisfaction with the results of reconstruction than those who received saline implants. This information can be used to optimize shared medical decision‐making by providing patients with realistic postoperative expectations. Cancer 2010. © 2010 American Cancer Society.     

Esophageal tumor length is independently associated with long‐term survival

BACKGROUND:

Esophageal cancer staging uses tumor depth as the sole criterion for assessment of the primary tumor (pT). To the authors' knowledge the impact of esophageal tumor length on long‐term outcome and the esophageal cancer staging system has not been fully evaluated in the current era.

METHODS:

All esophageal cancer patients (n = 209) undergoing surgery from 1995 to 2005 who did not receive preoperative chemotherapy or radiotherapy were reviewed. Maximum esophageal tumor length along a craniocaudal axis was determined pathologically after surgical resection. Univariate and multivariate analyses were used to assess the impact of esophageal tumor length (≤3 cm vs >3 cm) on long‐term survival.

RESULTS:

Esophageal tumor length was closely associated with long‐term survival (hazards ratio [HR] of 6.14 [95% confidence interval (95% CI), 4.1‐9.25]; 5‐year survival: ≤3 cm = 68%, >3 cm = 10% [P < .001]). Multivariate Cox regression analyses demonstrated tumor length (HR of 2.13 [95% CI, 1.26‐3.63]) was found to be a significant independent predictor of long‐term survival even when controlled for sex, age, tumor location, histology, margin positivity, surgical procedure, and current pTNM criteria. The incorporation of tumor length in pTNM staging significantly improves the ability to predict the long‐term survival of patients (5‐year survival for patients with tumors ≤3 cm and stages I, IIA, IIB, and III disease = 86%, 62%, 49%, and 22%, respectively; survival for patients with tumors measuring >3 cm and stages I, IIA, IIB, and III disease = 27%, 22%, 0%, and 8%, respectively [P < .1]).

CONCLUSIONS:

Esophageal tumor length is an independent predictor of long‐term survival in the current era and should be considered for incorporation into the current esophageal cancer staging system to better predict long‐term survival and identify high‐risk patients for postoperative therapy. Cancer 2009. © 2008 American Cancer Society.     

Optimizing locoregional control and survival for women with breast cancer: a review of current developments in postmastectomy radiotherapy

For women who opt for mastectomy as primary surgery in breast cancer, indications for adjuvant radiotherapy are also being redefined in light of evidence demonstrating that postmastectomy radiotherapy (PMRT), when given in conjunction with systemic therapy, improves, not only locoregional control, but also survival. However, in certain settings, particularly in patients wih intermediate-risk disease, and in some patients treated with neoadjuvant chemotherapy, the role of PMRT remains controversial. Here, the authors review modern data pertaining to the benefits and risks of PMRT and discuss controversies related to the indications for PMRT, focusing on patients with T1–2 breast cancer with 0–3 positive nodes and patients treated with neoadjuvant chemotherapy. They also summarize key issues related to the integration of PMRT with other treatment modalities.