Micrometastases or isolated tumor cells and the outcome of breast cancer.

BACKGROUND: The association of isolated tumor cells and micrometastases in regional lymph nodes with the clinical outcome of breast cancer is unclear. METHODS: We identified all patients in The Netherlands who underwent a sentinel-node biopsy for breast cancer before 2006 and had breast cancer with favorable primary-tumor characteristics and isolated tumor cells or micrometastases in the regional lymph nodes. Patients with node-negative disease were randomly selected from the years 2000 and 2001. The primary end point was disease-free survival. RESULTS: We identified 856 patients with node-negative disease who had not received systemic adjuvant therapy (the node-negative, no-adjuvant-therapy cohort), 856 patients with isolated tumor cells or micrometastases who had not received systemic adjuvant therapy (the node-positive, no-adjuvant-therapy cohort), and 995 patients with isolated tumor cells or micrometastases who had received such treatment (the node-positive, adjuvant-therapy cohort). The median follow-up was 5.1 years. The adjusted hazard ratio for disease events among patients with isolated tumor cells who did not receive systemic therapy, as compared with women with node-negative disease, was 1.50 (95% confidence interval [CI], 1.15 to 1.94); among patients with micrometastases, the adjusted hazard ratio was 1.56 (95% CI, 1.15 to 2.13). Among patients with isolated tumor cells or micrometastases, the adjusted hazard ratio was 0.57 (95% CI, 0.45 to 0.73) in the node-positive, adjuvant-therapy cohort, as compared with the node-positive, no-adjuvant-therapy cohort. CONCLUSIONS: Isolated tumor cells or micrometastases in regional lymph nodes were associated with a reduced 5-year rate of disease-free survival among women with favorable early-stage breast cancer who did not receive adjuvant therapy. In patients with isolated tumor cells or micrometastases who received adjuvant therapy, disease-free survival was improved.

Histological type is not an independent prognostic factor for the risk pattern of breast cancer recurrences.

Invasive lobular breast cancer (ILC) is less common than invasive ductal breast cancer (IDC) and appears to have a distinct biology. Inconsistent findings regarding disease-free survival (DFS) are probably due to the fact that histologic type is related to hormone receptor status. This study aims to determine whether the type of the primary breast cancer histology is an independent prognostic factor for DFS, the risk pattern of loco-regional recurrences and distant metastases (DM), and whether it is a prognostic factor for the site of DM. All Dutch women diagnosed between 2003 and 2005 with ILC (n = 2,949) or IDC (n = 22,378) were selected from the Netherlands Cancer Registry. DFS was assessed using proportional hazard regression analysis. Compared to patients with IDC, those with ILC were significantly older and more likely to have more than three positive lymph nodes and have larger, better differentiated, more multifocal, and hormone receptor positive tumors (all P < 0.001). ILC was more likely to metastasize to the gastrointestinal organs and bones and less likely to the lung, central nervous system, and lymph nodes. Within the ER+PR+ and ER+PR- subgroups ILC was still more likely to metastasize to gastrointestinal organs and less likely to the lung. The timing of recurrence was correlated to hormone receptor status, independent of histological type. Highest risks were observed among ER-PR- patients within 2 years of surgery. Multivariable analysis showed that histological type is not an independent significant prognostic factor of DFS for the first 3 years post-surgery and thereafter (<3 years HR 0.91, 95 % CI 0.78-1.06, >3 years HR 1.07, 95 % CI 0.88-1.30). Histological type should not be considered an important prognostic factor for the risk and risk pattern of recurrences.

The impact of social and personal resources on psychological distress in women at risk for hereditary breast cancer.

OBJECTIVE: The objectives of the present study were to (1) evaluate whether social and personal resources were independently related to psychological distress and (2) examine the interrelationships of social and personal resources in women at risk for hereditary breast cancer. METHODS: General and breast cancer specific distress, family communication regarding hereditary breast cancer, perceived social support, self-esteem, self-concept, and demographics were assessed in 222 high-risk women, having opted either for regular surveillance or prophylactic surgery. RESULTS: Structural equation modeling showed that (1) both personal and social resources were independently associated with psychological distress and (2) the associations between social resources and psychological distress were partially mediated by personal resources. Support from family and friends was associated with a higher level of self-esteem, which in turn was associated with less general distress. Furthermore, communication regarding cancer within the nuclear family was associated with decreased feelings of stigmatization, which in turn was associated with less general and breast cancer specific distress. Moreover, open communication within the family was associated with a reduced sense of vulnerability. CONCLUSION: Health workers involved in the care of high-risk women should carefully monitor women's personal and social resources, and if compromised refer them for appropriate support.

Psychological distress in women at risk for hereditary breast cancer: the role of family communication and perceived social support.

BACKGROUND: Hereditary breast cancer has a profound impact on individual family members and on their mutual communication and interactions. The way at-risk women cope with the threat of hereditary breast cancer may depend on the quality of family communication about hereditary breast cancer and on the perceived social support from family and friends. OBJECTIVE: To examine the associations of family communication and social support with long-term psychological distress in a group of women at risk for hereditary breast cancer, who opted either for regular breast surveillance or prophylactic surgery. METHODS: The study cohort consisted of 222 women at risk for hereditary breast cancer, who previously participated in a study on the psychological consequences of either regular breast cancer surveillance or prophylactic surgery. General and breast cancer specific distress, hereditary cancer-related family communication, perceived social support, and demographics were assessed. RESULTS: Using structural equation modelling, we found that open communication about hereditary cancer within the family was associated with less general and breast cancer specific distress. In addition, perceived support from family and friends was indirectly associated with less general and breast cancer-specific distress through open communication within the family. DISCUSSION: These findings indicate that family communication and perceived social support from friends and family are of paramount importance in the long-term adaptation to being at risk for hereditary breast cancer. Attention for these issues needs to be incorporated in the care of women at risk for hereditary breast cancer.

The contribution of self-esteem and self-concept in psychological distress in women at risk of hereditary breast cancer.

OBJECTIVE: Clarification of the role of several aspects of self-concept regarding psychological distress in women at risk of hereditary breast cancer will help to target counselling and psychosocial interventions more appropriately. In this study, we aimed (1) to examine the role of general self-esteem and specific aspects of self-concept (i.e. stigma, vulnerability, and mastery) in psychological distress in women at risk of hereditary breast cancer and (2) to compare the relative importance of these self-concept aspects in psychological distress in women with low versus high self-esteem. METHODS: General and breast-cancer-specific distress, self-esteem, self-concept, and demographics were assessed in 246 women being at risk of hereditary breast cancer, who opted either for regular breast surveillance or prophylactic surgery. RESULTS: In the total study group, self-esteem was negatively associated with general distress. Furthermore, feeling stigmatized was strongly associated with more breast-cancer-specific distress, and to a lesser degree with general distress. In women with low-self esteem, feelings of stigmatization were strongly associated with higher levels of both breast-cancer-specific and general distress, while a sense of mastery was associated with less general distress. For women with high self-esteem, feelings of both stigmatization and vulnerability were associated with more breast-cancer-specific distress, whereas there were no significant associations with general distress. DISCUSSION: Psychosocial interventions or support groups for women at risk of hereditary breast cancer should focus on self-esteem and feelings of stigmatization and isolation, and consequently tailor the interventions on specific items for respective women.

Prognostic factors in 77 curative chest wall resections for isolated breast cancer recurrence.

BACKGROUND: Full-thickness chest wall resection (CWR) is the preferred treatment for breast cancer (BC) patients with extensive isolated locoregional recurrence. It remains a challenge to select patients that will benefit most from this treatment. The aim of this study was to define prognostic factors in patients who undergo CWR with curative intent. METHODS: BC patients who underwent a CWR with curative intent for recurrence of disease between 1986 and 2006 were included in this retrospective study. Twenty-two factors were studied in a univariate analyses, and multivariate stepwise Cox regression analyses was performed. RESULTS: Seventy-seven patients were included in this study. The 5-year overall survival was 25%. There was one postoperative death. Univariate analyses showed that three prognostic factors were significantly correlated with OS and disease-free survival: (1) interval between primary treatment and CWR (P = .02 and .004, respectively), (2) chemotherapy for recurrence (P = .05 and .05, respectively), and (3) resection specimen smaller than 150 cm2 (P = .03 and .009, respectively). An interval lasting >10 years between primary treatment and CWR remained statistically significantly correlated with better overall survival and disease-free survival after multivariate analyses. CONCLUSIONS: CWR is a safe treatment in patients who have isolated extensive BC recurrence. The best survival outcome was seen in patients after a disease-free interval of >or= 10 years. Existing data show that adjuvant radiotherapy and adjuvant hormone therapy for estrogen-positive tumors improves overall survival. Neoadjuvant chemotherapy may be considered in individual patients.

Prophylactic mastectomy in BRCA1/2 mutation carriers and women at risk of hereditary breast cancer: long-term experiences at the Rotterdam Family Cancer Clinic.

BACKGROUND: BRCA1/2 mutation carriers and women from a hereditary breast(/ovarian) cancer family have a highly increased risk of developing breast cancer (BC). Prophylactic mastectomy (PM) results in the greatest BC risk reduction. Long-term data on the efficacy and sequels of PM are scarce. METHODS: From 358 high-risk women (including 236 BRCA1/2 carriers) undergoing PM between 1994 and 2004, relevant data on the occurrence of BC in relation to PM, complications in relation to breast reconstruction (BR), mutation status, age at PM and preoperative imaging examination results were extracted from the medical records, and analyzed separately for women without (unaffected, n = 177) and with a BC history (affected, n = 181). RESULTS: No primary BCs occurred after PM (median follow-up 4.5 years). In one previously unaffected woman, metastatic BC was detected almost 4 years after PM (primary BC not found). Median age at PM was younger in unaffected women (P < .001), affected women more frequently were 50% risk carriers (P < .001). Unexpected (pre)malignant changes at PM were found in 3% of the patients (in 5 affected, and 5 unaffected women, respectively). In 49.6% of the women opting for BR one or more complications were registered, totaling 215 complications, leading to 153 surgical interventions (71%). Complications were mainly related to cosmetic outcome (36%) and capsular formation (24%). CONCLUSIONS: The risk of developing a primary BC after PM remains low after longer follow-up. Preoperative imaging and careful histological examination is warranted because of potential unexpected (pre)malignant findings. The high complication rate after breast reconstruction mainly concerns cosmetic issues.

Most women recover from psychological distress after postoperative complications following implant or DIEP flap breast reconstruction: A prospective long-term follow-up study.

BACKGROUND: Substantial complication rates after postmastectomy breast reconstruction (BR) in breast cancer patients have been reported. Few studies have reported on the resulting psychological distress (PD) and satisfaction with the aesthetic result in relation to postoperative complications after completion of implant or DIEP flap BR. The present study investigated whether women were able to recover from complication related distress in the long term. METHODS: PD was prospectively measured using questionnaires regarding anxiety, depression and cancer distress. Eligible patients completed questionnaires before BR (T0, n = 144), after one month (T1, n = 139) and after completion of BR, approximately 21 months after initial reconstructive surgery (T2, n = 119). Satisfaction with the aesthetic result was assessed 21 months after BR. Data concerning complications, subsequent additional surgery and total reconstruction failure up to T2 were collected from the medical records. Analyses were performed using multi-level regression analyses correcting for age. RESULTS: One or more complications occurred in 61 patients (42%) and 50 women required subsequent surgery (35%). In time, mean PD significantly declined towards baseline scores independent of complications. However, a total reconstruction failure (n = 10) was significantly associated with a large temporary increase in depression scores. After additional surgery due to complications patients were less satisfied with aesthetic outcome, although patient satisfaction was independent of PD. CONCLUSIONS: PD outcomes generally declined to normal levels after completion of the entire BR course. Patients experiencing a total reconstruction failure reported more depression after this loss, but in the long term recovered to the same level as women without complications. These findings indicate that women generally can cope efficiently with these serious adverse events, even if they were less satisfied with the aesthetic result.

Body image issues after bilateral prophylactic mastectomy with breast reconstruction in healthy women at risk for hereditary breast cancer.

The outcome of bilateral prophylactic mastectomy with breast reconstruction (BPM-IBR) in healthy BRCA1/2 mutation carriers can be potentially burdensome for body image and the intimate relationship. Therefore, in the current analysis the impact on body image, sexual and partner relationship satisfaction was prospectively investigated in women opting for BPM-IBR as well as cancer distress and general quality of life. Healthy women undergoing BPM-IBR completed questionnaires preoperatively (T0, n = 48), at 6 months (T1, n = 44) and after finishing breast reconstruction (median 21 months, range 12-35) (T2, n = 36). With multi-level regression analyses the course of outcome variables was investigated and a statistically significant change in body image and/or sexual and partner relationship satisfaction was predicted by baseline covariates. Body image significantly decreased at T1. At T2 sexual relationship satisfaction and body image tended to be lower compared to baseline. The overall partner relationship satisfaction did not significantly change. At T2, 37 % of the women reported that their breasts felt unpleasantly, 29 % was not satisfied with their breast appearance and 21 % felt embarrassed for their naked body. Most body image issues remained unchanged in 30 % of the women. A negative body image was predicted by high preoperative cancer distress. BPM-IBR was associated with adverse impact on body image in a substantial subgroup, but satisfaction with the overall sexual and partner relationship did not significantly change in time. The psychosocial impact of BPM-IBR in unaffected women should not be underestimated. Psychological support should ideally be integrated both before and after BPM-IBR.

Efficacy of cognitive behavioral therapy and physical exercise in alleviating treatment-induced menopausal symptoms in patients with breast cancer: results of a randomized, controlled, multicenter trial.

PURPOSE: The purpose of our study was to evaluate the effect of cognitive behavioral therapy (CBT), physical exercise (PE), and of these two interventions combined (CBT/PE) on menopausal symptoms (primary outcome), body image, sexual functioning, psychological well-being, and health-related quality of life (secondary outcomes) in patients with breast cancer experiencing treatment-induced menopause. PATIENTS AND METHODS: Patients with breast cancer reporting treatment-induced menopausal symptoms (N=422) were randomly assigned to CBT (n=109), PE (n=104), CBT/PE (n=106), or to a waiting list control group (n=103). Self-report questionnaires were completed at baseline, 12 weeks, and 6 months. Multilevel procedures were used to compare the intervention groups with the control group over time. RESULTS: Compared with the control group, the intervention groups had a significant decrease in levels of endocrine symptoms (Functional Assessment of Cancer Therapy-Endocrine Symptoms; P<.001; effect size, 0.31-0.52) and urinary symptoms (Bristol Female Lower Urinary Tract Symptoms Questionnaire; P=.002; effect size, 0.29-0.33), and they showed an improvement in physical functioning (36-Item Short Form Health Survey physical functioning subscale; P=.002; effect size, 0.37-0.46). The groups that included CBT also showed a significant decrease in the perceived burden of hot flashes and night sweats (problem rating scale of the Hot Flush Rating Scale; P<.001; effect size, 0.39-0.56) and an increase in sexual activity (Sexual Activity Questionnaire habit subscale; P=.027; effect size, 0.65). Most of these effects were observed at both the 12-week and 6-month follow-ups. CONCLUSION: CBT and PE can have salutary effects on endocrine symptoms and, to a lesser degree, on sexuality and physical functioning of patients with breast cancer experiencing treatment-induced menopause. Future work is needed to improve the design and the planning of these interventions to improve program adherence.

Women's motives to opt for either implant or DIEP-flap breast reconstruction.

OBJECTIVE: Understanding women's motives concerning breast reconstructive surgery will contribute to a better counselling and care for the increasing number of women choosing post-mastectomy breast reconstruction (BR). METHODS: We interviewed 31 women who opted for implant or deep inferior epigastric perforator (DIEP)-flap BR after therapeutic or prophylactic mastectomy. Motives for BR in general and for the selected type of BR were investigated following a phenomenological qualitative research approach. RESULTS: Women opting for implant BR were concerned with surgery-related issues, such as recovery time, number of scars and impact of surgery. They wanted to return to their daily life and restore their body image as soon as possible. Patients choosing DIEP-flap BR were more focussed on regaining a natural breast and wanted to benefit from the advantages of autologous tissue. Women scheduled for prophylactic mastectomy saw BR as an integral part of their treatment. Patients opting for BR after therapeutic mastectomy wanted to regain a complete body image with BR. CONCLUSIONS: Patients' motives for implant BR were primarily related to surgical issues, whereas women who chose DIEP-flap BR especially focussed on regaining a breast that resembles their own lost breast as well as possible. Clinical variables (such as therapeutic or prophylactic mastectomy, breast irradiation, and waiting lists) need to be taken into account when considering a certain type of BR, as these can be of great importance in the decision-making process.

[Suppose a mammary carcinoma is absent from the surgical specimen]. / Stel dat het mammacarcinoom ontbreekt in het resectiepreparaat.

In three women aged 53, 51, and 42 respectively, who were treated by breast-conserving surgery for mammary carcinoma, the cancer was not found in the surgical specimen. For both patient and treating physician it is rather worrying when there is no good explanation for the fact that a histologically proven breast cancer cannot be detected in the surgical specimen without neoadjuvant therapy having been given. It is important to revise the needle biopsies, to exclude mix up of patient materials, to totally include the resected specimen in the pathological examination and to perform addition imaging of the remaining breast, preferably with MRI. An explanation may be that biopsy has removed such an amount of tumour tissue that the remains are not found. If no flaws are apparent, adjuvant radiotherapy and further adjuvant therapy on indication suffices.

Standard psychological consultations and follow up for women at increased risk of hereditary breast cancer considering prophylactic mastectomy.

BACKGROUND: Women at increased (genetic) risk of breast cancer have to weigh the personal pros and cons of prophylactic mastectomy (PM) as an option to reduce their cancer risk. So far, no routine referral to a psychologist has been investigated for women considering PM. Aim of this study was to asses: 1) the acceptance of the offer of a standard psychological consultation as part of pre-surgical decision-making in high-risk women, 2) reasons for PM and reasons for postponing it, 3) the need for additional psychological interventions, and factors associated, and 4) the frequency of psychiatric/psychological treatment history. METHODS: During a 30 months period, women at high risk considering PM were offered a psychological consultation. The content of these, and follow-up, consultations were analyzed. RESULTS: Most women (70 out of 73) accepted the psychological consultation, and 81% proceeded with PM. Main reasons for undergoing PM were to reduce anxiety about cancer, and to reduce the cancer risk. Uncertainty about surgery and the need for further information were the reasons given most frequently for postponing PM. Additional psychological support was given to 31% before and 14% after PM. The uptake of additional support was significantly higher in women with a BRCA1/2 mutation. A history of psychiatric/psychological treatment was present in 36%, mainly consisting of depression and grief after death of a mother. CONCLUSION: The uptake-rate of the standard psychological consultation indicates a high level of acceptability of this service for women deciding about PM. Since anxiety is one of the main reasons for considering PM, and depression and grief were present in a third, a standard consultation with a psychologist for high-risk women considering PM may be indicated. This may help them arrive at an informed decision, to detect and manage psychological distress, and to plan psychological support services.

Sensitivity to first-line chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers.

PURPOSE: Preclinical as well as a few small retrospective, neoadjuvant studies suggest that breast cancer (cells) without functional BRCA1 or BRCA2 protein have an increased sensitivity to some chemotherapeutic agents causing double-strand DNA breaks. In this study we assessed the sensitivity to standard first-line chemotherapy of metastatic BRCA1/2-associated breast cancer, compared with sporadic breast cancer patients. PATIENTS AND METHODS: From the Family Cancer Clinic database, we selected 93 BRCA1- and 28 BRCA2-associated breast cancer patients treated with chemotherapy for metastatic disease before January 1, 2007. Objective response (OR), progression-free survival (PFS), and overall survival (OS) after start of first-line chemotherapy were compared with those of sporadic patients, matched for year of birth, age at diagnosis of primary breast cancer, and year of detection of metastatic disease. RESULTS: The chemotherapy regimens most frequently used were anthracycline-based (n = 147) and cyclophosphamide, methotrexate, and fluorouracil (CMF)/CMF like (n = 68). As compared to sporadic patients, BRCA2-associated patients had a significantly higher OR (89% v 50%; P = .001), a longer PFS (hazard ratio multivariate [HR(mult)] 0.64; P = .04) and a prolonged OS (HR(mult), 0.53; P = .005) after start of first-line chemotherapy for metastatic breast cancer. For BRCA1-associated patients, a nonsignificant trend for an increased OR (66% v 50%; P = .07), and a longer PFS (HR(mult), 0.79; P = .14) after first-line chemotherapy for metastatic breast cancer was observed, but not for OS. CONCLUSION: BRCA2-associated breast cancer is more sensitive to standard first-line chemotherapy for metastatic breast cancer in comparison with sporadic breast cancer, especially to anthracyclines. For BRCA1-associated breast cancer no statistically significant higher sensitivity was observed.

Distant disease-free interval, site of first relapse and post-relapse survival in BRCA1- and BRCA2-associated compared to sporadic breast cancer patients.

BACKGROUND: Data on distant disease-free interval (DDFI) and the localization of the first distant metastasis (DM) in BRCA1- and BRCA2-associated breast cancer (BC) patients are as yet scarcely available. PATIENTS AND METHODS: We identified 57 BRCA1-associated and 31 BRCA2-associated BC patients, diagnosed between 1980 and 2001, and developing DM disease before 2004, July 1. DDFI, the site(s) of first DM and post-relapse survival of these patients were compared with those of 192 sporadic BC patients. RESULTS: As compared to sporadic patients, BRCA1 patients developed less often bone DM (30% vs. 51%; P = 0.005), but tended to develop more often lung DM (26% vs. 16%; P = 0.07), and DM at multiple sites (44% vs. 32%; P = 0.11). In BRCA2-associated compared to sporadic patients, first DM more commonly occurred in lymph nodes (23% vs. 7%; P = 0.007) and at multiple sites (48% vs. 32%; P = 0.08). Adjuvant systemic therapy appeared to be most effective in BRCA2 mutation carriers. Post-relapse survival was worse for BRCA1- and better for BRCA2-associated patients as compared to sporadic patients, but differences disappeared after adjustment for ER-status, site of first DM and DDFI. CONCLUSION: The site of first DM is different between BRCA1- and BRCA2-associated and sporadic BC patients. Differences in post-relapse survival could be explained by differences in site of first DM, in ER-status and in DDFI. Treatment efficacy may differ dependent on genetic status.