Use of Palliative Endocrine Therapy in Patients with Hormone Receptor-Positive Distant Metastatic Breast Cancer: How Often, How Effective, How Long?

BACKGROUND: This study provides real-world clinical evidence regarding palliative endocrine therapy (ET) in breast cancer (BC). The main questions to be answered were: how often and how long did patients receive ET? A particular aspect was the analysis of compliance and persistence with ET. METHODS: An analysis of a nonselected/consecutive cohort of women with distant metastatic hormone receptor-positive BC (n = 205) was conducted. RESULTS: In all, 165 patients (80.5%) received ET during the palliative disease course. The noncompliance rate was 1.5%. Sixty-seven patients (40.6%) had ET as the only antineoplastic therapy. The median number of therapy lines was 2, and the median duration was 18 months. The median metastatic disease survival (MDS) was 34 months. In patients who had an MDS of ≥9 months (n = 145; 87.9%), during 70.6% of the MDS time only ET had been administered. Patients who were naïve to ET more often had a good response to and a longer duration of palliative ET than those who were not. The nonpersistence rate was 4.3%. CONCLUSIONS: Excluding the few patients who had a rapidly progressive course, the disease was controlled for about 70% of the entire palliative disease course with ET alone. Only very few patients were nonpersistent with ET and consciously stopped a still effective, ongoing ET.

Unintended pregnancy during the first year after breast cancer diagnosis.

OBJECTIVES: Young women experience high levels of anxiety and distress during cancer diagnosis and therapy, and it can be devastating to become pregnant in this vulnerable state. Pregnancy during cancer treatment is strongly discouraged, as radiotherapy and chemotherapy administered during the first trimester of pregnancy result in increased congenital malformations. METHODS: In this study, we analysed an unselected, consecutive cohort of young breast cancer (BC) patients with regard to unintended pregnancy during the first year after BC diagnosis. We analysed all patients who were ≤40 years of age at initial BC diagnosis (n = 100, mean age at diagnosis: 35.9 years), according to data from the Basel Breast Cancer Database. The frequency of unintended pregnancy was assessed, and particular attention was given to patients' obstetric and reproductive history. RESULTS: Forty-two percent of the cohort (mean age 36.5 years) were identified as not at risk of unintended pregnancy during the first year after BC diagnosis. However, 58% of the cohort (mean age 35.6 years) were using an ineffective contraceptive method and thus were at risk of unintended pregnancy. The rate of unintended pregnancy was 3.5% in this group (two patients). Oncologists should be aware that the use of reliable contraception should be discussed before starting, and also during, adjuvant therapy. CONCLUSIONS: Oncologists should consider actively referring young BC patients to a gynaecologist to ensure proper contraceptive counselling.

Epidemiology in ovarian carcinoma: Lessons from autopsy.

OBJECTIVE: We challenge epidemiologic knowledge regarding ovarian carcinoma (OC) by bridging the gap between clinical and autopsy data. METHODS: Autopsy reports, histological slides and clinical files from 660 patients in whom OC was diagnosed from 1975-2005 were studied (autopsy cohort, n=233; Clinical Cancer Registry from the local gyneco-oncologic center, n=427). RESULTS: Out of the autopsy cohort, we identified four distinct subgroups of patients: 1) OC was diagnosed before autopsy, n=156 (67.0%). 2) OC was an incidental finding, n=16 (6.8%). 3) The ovarian tumors were not primary OC but rather metastases from other primary tumors; this revised diagnosis was first made by using current histopathological knowledge/techniques, n=24 (10.3%). 4) Death was directly due to OC in its final stage and OC was first diagnosed by autopsy, n=37 (15.9%); when these cases were added to the Clinical Cancer Registry to an adjusted OC incidence model, the autopsy cases comprised 8.8% of the adjusted cohort and almost doubled the percentage of oldest patients (≥80 years at diagnosis) from 4.9% to 9.3% (p=0.013). CONCLUSIONS: Epidemiological data from the 1970s-1990s may overestimate true incidence because up to 10% of carcinomas in the ovary were not properly classified. Patients who were first diagnosed with OC by autopsy comprise a distinct subgroup. These are patients who have not been seen by specialized oncologists and thus play no role in their perception of the disease. Nevertheless, these cases have impact on prevalence and incidence data of OC and in an era of reduced autopsy rates will probably be overlooked.

Personal or first-degree family breast cancer history: which has higher impact on tumor detection and tumor size in breast cancer.

PURPOSE: A woman's risk of developing breast cancer (BC) is increased if she has a personal history (PH) or family history (FH) of the disease. We compared the impact of the two risk factors PH and FH on tumor detection and tumor size at diagnosis in a cohort of BC patients. METHODS: The study cohort comprised 1,037 invasive BC patients (≤70 years at diagnosis). From these, 92 patients (8.5%) had a positive PH and 151 patients (13.7%) had a positive first-degree FH. RESULTS: Compared to the tumors of patients without PH or FH, the lesions of patients who had a positive PH or a positive FH were more often found by radiologic breast examinations (RBE) (PH: 49.4%, FH: 43.4%, no PH/FH: 26.2%; both comparisons p < 0.001). In patients with a positive FH, the tumors were slightly less often found by RBE as in patients with a positive PH (p = 0.468). Patients with a positive PH or FH had smaller tumors compared with those without such a history (PH: 19.7 mm, FH: 19.6 mm, no PH/FH: 26.7 mm; p = 0.015/p < 0.001). The tumor sizes of patients with a positive PH were almost identical to those of patients with a positive FH (p = 0.999). CONCLUSIONS: In women with a positive FH or PH of BC, the increased awareness of BC risk led to the detection of smaller tumors compared to women who have not had this experience. However, comparison of the two risk factors showed that they had a similar impact on the RBE detection rate of BC lesions and that the tumor sizes were nearly identical.

Breast cancer in women 80 years of age and older: a comprehensive analysis of an underreported entity.

BACKGROUND: Approximately 10% of breast cancer (BC) patients are over the age of 80. We present the first comprehensive review on this particular group of patients. PATIENTS AND METHODS: The treatments and disease courses of an unselected cohort of patients, whose age at first diagnosis was ≥ 80 years (n = 151), were compared to those of a group of women, who were aged 56-66 years (n = 372). RESULTS: The group of elderly patients had larger tumors at first diagnosis (25 mm vs. 18 mm, p < 0.001) and higher disease stages (I: 31.1% vs. 44.1%, IV: 11.9% vs. 5.4%; each p < 0.001). There were no significant differences between both groups in terms of histologic subtype, grading, hormonal receptor status and HER2 status. The tumors of older patients were more often detected by clinical examination (38.9% vs. 17.0%, p < 0.001) and less often by mammography/sonography (10.4% vs. 29.9%, p < 0.001). The rate of patients who died of BC were similar in both groups (21.2% vs. 21.5%, p = 1.00). In the patients who had no evidence of metastases and who opted for primary non-surgical management (n = 21), the tumor could be stabilized without considerable morbidity in only 42.9%. Persistence to adjuvant endocrine therapy was comparable (83.0% vs. 88.3%, p = 0.357). In the adjuvant as well as in the palliative settings, elderly patients received less chemotherapy than younger ones (adjuvant: 1.6% vs. 23.3%; palliative: 32.3% vs. 68.4%; each p < 0.001). For palliative treatments only, elderly patients received fewer treatment regimens (≥ 3 therapy lines: 16.0% vs. 54.9%, p < 0.001). In those patients who died of BC, elderly women had inferior overall (25 vs. 54.5 months, p < 0.001) as well as metastatic-disease survival (11.5 vs. 19 months, p = 0.062). CONCLUSION: It must be ensured that appropriate standard therapies should not be routinely withheld in older patients based on erroneous perceptions regarding the biological nature of BC in the elderly and lack of knowledge about available therapy regimens. Physicians should consider that preservation of current life circumstances and maintenance of quality of life are frequently more important than "classical" hard medical facts such as survival times.

Impact of overweight and obesity on postmenopausal breast cancer: analysis of 20-year data from Switzerland.

PURPOSE: Greater body fatness has been identified as a risk factor for postmenopausal breast cancer. For countries with low overweight/obesity rates, data on prevalence and time course of overweight/obesity in women with breast cancer in comparison to women in the general population is limited. The Swiss female population is distinctive for two reasons: (a) low rates of overweight/obesity compared with other western countries, and (b) no obesity epidemic, i.e. stable rates of overweight/obesity for more than 10 years. METHODS: Overweight and obesity were analyzed in 51 to 80-year-old breast cancer patients initially diagnosed between 1990 and 2009. Patient data was derived from the Basel Breast Cancer Database (BBCD). This data was compared with the data of women of the same age from the four Swiss Health Surveys (SHS) conducted between 1992 and 2007. Differences between measured (BBCD) and self-reported (SHS) data were corrected using equations approved for the Swiss population. RESULTS: Of 958 postmenopausal BBCD patients, 32% were overweight and 20% were obese. Of the 14,476 women of the SHS, 38% were overweight and 17% were obese. In the BBCD, there was no change in the prevalence of overweight/obesity over the last 20 years. The four SHS show a convex curvature for obesity, i.e. a transient increase. No significant differences were observed between BBCD and corrected SHS data for overweight and obesity during this period. CONCLUSIONS: In this Swiss study group with a comparably low prevalence of overweight and obesity, no association between body fatness and postmenopausal breast cancer was observed.

Is the current concept of recurrent ovarian carcinoma as a chronic disease also applicable in platinum resistant patients?

PURPOSE: The treatment of recurrent ovarian carcinoma (ROC) has become increasingly oriented according to the therapy principles of a chronic disease. We evaluated whether it is justifiable to also apply this concept to the treatment of platinum resistant patients with their known poor prognosis and short overall survival (OS). METHODS: We analyzed the overall courses of 85 unselected ROC patients and defined the following groups: A, platinum resistant patients (n=39); subgroup A.1, those who received no or at maximum one line of palliative chemotherapy (n=15, 38.5%); subgroup A.2, those who received>or=two therapy lines (n=24, 61.5%); B, platinum sensitive patients, n=46. RESULTS: Group A had significantly lower OS than group B (median: 16 vs. 25 months; p=0.019). Group A.1 had significantly worse outcome compared to group A.2 (median: 5 vs. 21.5 months; p<0.001). The comparison between study group A.2 and group B showed comparable survival rates (p=0.738). Considering only the patients who had completed treatment courses, the median number of therapy lines administered was higher in group A.2 than in group B (4 vs. 3; p=0.008). CONCLUSIONS: There is not only the known dichotomy between platinum sensitive and resistant ROC patients, but rather also within the platinum resistant subgroup itself. There is a considerably large subgroup of platinum resistant patients who will subsequently enter a phase where multiple treatment programs will be considered and administered. These patients have similar survival rates compared to those from the platinum sensitive patient group and the therapy principles of a chronic disease are applicable.

Three-dimensional pathological size assessment in primary breast carcinoma.

Maximal tumor diameter (MD) is traditionally an important prognostic factor in breast cancer. It must be questioned, however, how well a one-dimensional parameter alone can represent the actual morphologic condition of a three-dimensional body. Along with the pathologically assessed MD and two perpendicular diameters (PDs) of a lesion, eccentricity (EF) and the three-dimensional parameters tumor volume (TV) and surface area (TSA) of 395 ductal invasive breast carcinomas of limited size (10-40 mm) were calculated. The dependent prognostic variable was axillary lymph node involvement (ALNI). MD, TV and TSA area were highly significant predictors of ALNI; these variables had similar levels of prediction accuracy (univariate analyses: MD: P = 0.0003, TV: P = 0.0009, TSA: P < 0.0001; multivariate analyses: MD: P = 0.0018, TV: P = 0.0109, TSA: P = 0.0009; pseudo R-squared values: MD: 0.42, TV: 0.39, TSA: 0.39). Despite certain variations in tumor shape, TV and TSA with similar MD, there is no evidence that three-dimensional pathologic measurements (TV/TSA) are more precise prognostic predictors of ALNI compared to the one-dimensional measurement alone.

Systemic therapy of metastatic breast cancer: the truth beyond the clinical trials.

OBJECTIVE: To depict a clear and coherent picture of the overall course of palliative treatment in an unselected study cohort over the course of time. METHODS: We compared therapy type and course of 242 women whose distant metastatic disease was diagnosed from 1990 to 2006 and who ultimately died of the disease. We divided the patients into two subgroups depending on the year of diagnosis of metastases (group A: 1998-2006 vs. group B: 1990-1997). RESULTS: In both subgroups, there were no significant differences in the general type of treatment and the number of administered therapy lines (no systemic therapy: 12.9 vs.13.7%, p = 0.848; endocrine therapy only: 20.4 vs. 25.2%, p = 0.430; chemotherapy only: 18.4 vs.16.9%, p = 0.735; sequential combination regimen including endocrine therapy/chemotherapy/trastuzumab: 46.9 vs. 44.2%, p = 0.694; median: 2 lines). In the cases where chemotherapy was administered, there were no differences between the number of lines among older and younger patients (median: two lines; >or=70 years vs. <70 years: p = 0.269). The median metastatic disease-specific survival increased from 16 months in the period from 1990 to 1997, to 21 months in the period from 1998 to 2000 (p = 0.062). CONCLUSION: The number of patients who died from metastatic breast cancer without receiving any antineoplastic therapy was surprisingly high. The use of newer agents and regimens in the treatment of metastatic breast cancer was associated with an improved survival over time. Chemotherapy is a feasible option also among older patients.

Systemic therapy developments and their effects regarding the current concept of recurrent ovarian carcinoma as a chronic disease.

PURPOSE: To demonstrate how the current concept of recurrent ovarian carcinoma (ROC) as a chronic disease resulted in developments in the systemic treatment strategies and outcome over time. METHODS: We compared therapy type and course of a population-based cohort whose recurrent disease was diagnosed from 1990 to 2006. We divided the patients into two subgroups depending on the year of diagnosis of ROC (group A 1990-1997, n = 70; group B 1998-2006, n = 63). RESULTS: Both study groups showed similar results in survival (median recurrent disease-specific survival-A 18 months vs. B 19 months; P = 0.549). In group B, the patients had significantly fewer combination therapies administered [12.0% vs. 24.1%; odds ratio (OR) 0.43; 95% confidence interval (CI) 0.23-0.81; P = 0.0057], received more therapy lines (> or =3 lines 56.1% vs. 31.1%; OR 3.10; 95% CI 1.37-7.17; P = 0.005) and had significantly longer times of treatment (TT) in relation to the survival time (ST; mean TT/ST-ratio 57.5% vs. 47.5%; difference of the mean values B-A = -10.02; 95%CI -17.99 to -2.05; P = 0.014). CONCLUSIONS: The finding that survival of ROC patients could not be improved over time should not necessarily be viewed with undue pessimism regarding the general therapy situation. In the more recent study period, a similar outcome could be achieved with less aggressive treatment regimens, i.e., with fewer combination therapies and with longer treatment periods using less toxic agents. When a disease which requires periodic chemotherapy to control progressive course is increasingly treated with a strategy that permits stabilization with limited cumulative toxicity, then the requirements of a chronic disease management have been fulfilled.

Contraception counseling for young breast cancer patients: A practical needs assessment and a survey among medical oncologists.

BACKGROUND/METHODS: We analyzed an unselected, consecutive cohort of young breast cancer (BC) patients (≤40 years, n = 100) with regard to the contraceptive methods used at the time of diagnosis. Based on this data, we assessed the individual need for contraceptive counseling before cancer therapy. Secondly, in a study-specific self-report questionnaire, we surveyed 101 medical oncologists with the aim of evaluating attitudes towards contraception and how young patients are being counseled in the practical clinical setting. RESULTS: In 62% of our cohort of young BC patients, we identified situations in which contraceptive counseling was necessary at the time of BC diagnosis. The patients did not use contraception or used an ineffective method (TIER III/IV, 42%), or were using hormonal methods (12%) or IUDs (8%). Almost all respondents of the survey (99%) stated that contraception is an important aspect in the surveillance of young BC patients and the vast majority (90%) discussed this item before starting therapy. Only 20% of the respondents reported that they a) inform the patients that reliable contraception is necessary before starting therapy, b) ask whether contraceptive methods are used during ongoing therapy, and c) regularly refer their patients to specialist counseling by a gynecologist. CONCLUSIONS: A large proportion of young women require contraceptive counseling after newly diagnosed BC. Oncologists should be aware that the use of reliable contraceptive methods should not only be discussed before starting therapy, but also during ongoing therapy. Oncologists should consider actively referring their young patients to gynecologists to ensure proper contraceptive counseling.

Family ties: young breast cancer patients and their children.

BACKGROUND: This study assessed the interaction of "family ties" in a cohort of young breast cancer patients. METHODS: Based on the Basel Breast Cancer Database, we analysed an unselected, consecutive cohort of patients who were ≤40 years at breast cancer diagnosis (n = 100). RESULTS: Sixty patients had children at the time of diagnosis (mean number of children: 1.03). Only four patients had desired children after BC therapy. The average age of the children at breast cancer diagnosis of their mother was 7.7 years. The mean age of the children whose mothers died of breast cancer at the time of their mother's death was 13.1 years; these children (n = 37) lived an average of 84.7 months with the illness of their mother. Parity status was not a significant factor for compliance/persistence to adjuvant chemotherapy (p = 1.00). Patients who had children were more likely to be compliant/persistent to endocrine therapy (p = 0.021). Out of these patients, 41.2% rejected or discontinued endocrine therapy with the explicit intention to get pregnant. CONCLUSIONS: Desire for children was an important factor in refusing endocrine therapy. This clearly highlights the enormous pressure that many young women face in this situation. About a third of the children whose mothers were diagnosed with breast cancer experienced the palliative situation and the death of their mother. Since many of these children are confronted with a cancerous disease of their mothers during half of their childhood, special attention should be paid to age-appropriate support of a child in all phases of the mother's disease.

Self-detection and clinical breast examination: comparison of the two "classical" physical examination methods for the diagnosis of breast cancer.

UNLABELLED: This is the first comprehensive analysis comparing specific aspects of tumor detection between the two "traditional" breast cancer detection methods self-detection (SD) and clinical breast examination (CBE). a) Which method is better in detecting smaller tumors? Both methods showed similar mean tumor diameters (SD: 22.1 mm vs. CBE: 21.9 mm; p = 0.991). b) Different frequency distributions of tumor locations would indicate that certain locations in the breast are more difficult to palpate: comparison of both methods showed comparable results (p = 0.835). c) General differences in tumor sizes with regard to certain locations would be of importance because the patients and/or the physicians could be educated to pay particular attention to certain locations during physical examination, where larger tumors tend to be found: tumors located in the central region were with 25.0 mm significantly larger than those in the peripheral regions of the breast (superior: 21.6 mm, p = 0.001; inferior: 21.6 mm, p = 0.015; lateral: 21.9 mm, p = 0.002; medial (20.9 mm, p = 0.001). Tumor sizes within the four peripheral regions did not differ significantly. d) Patients whose tumors were found by CBE were older than those whose tumors were found by SD (67 years vs. 60 years, p < 0.001). CONCLUSION: annual CBE should be an integral part of general medical care in older women.

Radiotherapy in patients with distant metastatic breast cancer.

BACKGROUND: The study evaluates frequency of and indications for disease-related radiotherapy in the palliative breast cancer (BC) situation and analyzes in which phase of the palliative disease course radiotherapy was applied. PATIENTS & METHODS: 340 patients who developed distant metastatic disease (DMD) and died (i.e. patients with completed disease courses) were analyzed. RESULTS: 165 patients (48.5%) received palliative radiotherapy (255 series, 337 planning target volumes) as a part of palliative care. The most common sites for radiotherapy were the bone (217 volumes, 64.4% of all radiated volumes) and the brain (57 volumes, 16.9%). 127 series (49.8%) were performed in the first third of the metastatic disease survival (MDS) period; 84 series (32.8%) were performed in the last third. The median survival after radiotherapy was 10 months. Patients who had received radiation were younger compared to those who had no radiation (61 vs. 68 years, p < 0.001) and had an improved MDS (26 vs. 14 months, p < 0.001). Compared to rapidly progressive disease courses with short survival times, in cases where effective systemic therapy achieved a longer MDS (≥24 months), radiotherapy was significantly more often a part of the multimodal palliative therapy (52.1% vs. 37.1%, p = 0.006). CONCLUSIONS: In a cohort of BC patients with DMD, nearly one half of the patients received radiotherapy during the palliative disease course. In a palliative therapy approach, which increasingly allows for treatment according to the principles of a chronic disease, radiotherapy has a clearly established role in the therapy concept.

Primary and secondary distant metastatic breast cancer: two sides of the same coin.

OBJECTIVES: This study evaluated the differences between breast cancer (BC) patients who present with primary distant metastatic disease (PMD) and those who develop distant metastases during the course of their illness (secondary metastatic disease [SMD]) with regard to clinicopathological characteristics, patterns of metastatic sites, palliative therapy and survival. PATIENTS & METHODS: Based on a cohort of patients with newly diagnosed BC (n = 1459), we analyzed all patients who had PMD (n = 92, 6.3%) and those who developed SMD (n = 277, 20.3%). RESULTS: There were no significant differences with regard to the patient's age in which metastatic disease had been diagnosed (PMD/SMD: 64 years/66 years, p = 0.19). The SMD group had more often triple-negative carcinomas (25.5%/7.3%, p = 0.019); there were no significant differences with regard to grading (p = 0.61), HER2 status (p = 0.67) and hormonal receptor status (p = 1.00). The mean number of metastatic locations was similar (2.3/2.3, p = 0.91). While patients with PMD usually initiated systemic therapy, patients with SMD received systemic therapy after diagnosis of metastatic disease less often (16.4%/2.6%, p < 0.001). Both groups received palliative chemotherapy similarly often (PMD/SMD: 62.8%/63.3%, p = 1.00). The mean number of palliative therapy lines was similar (PMD/SMD: 2.8/3.2, p = 0.39). Compared to patients with SMD, patients who had PMD had a significantly improved metastatic disease survival (p < 0.001). The one-year, two-year and five-year survival rates were as follows: 76.9%/60.3%, 58.2%/43.0%, 23.1%/10.6%. The median survival times were 18.5 months and 32 months. CONCLUSION: The poorer prognosis of patients with SMD may be explained by differences in clinicopathological features of the tumor, metastatic patterns, the use palliative therapy and drug resistance of the tumor cells which occurs in therapy-naïve PMD patients at a later phase of the disease course.

The impact of overweight and obesity on breast cancer: data from Switzerland, so far a country little affected by the current global obesity epidemic.

This review presents results from the project "The Impact of Overweight/Obesity on Breast Cancer: data from Switzerland". Swiss data is interesting because the general female population is distinctive in two areas when compared to that of most other industrialized countries: Switzerland has comparatively low rates of overweight (22-23%) and obesity (7-8%) and has rather stable rates of overweight and obesity. The entire project comprised three major issues: (I) etiology of breast cancer (BC). There is a consistently shown association between obesity and postmenopausal BC risk in countries with high obesity prevalence rates in the literature. In our Swiss study group, however, we did not find higher rates of overweight and obesity in postmenopausal BC cases than in the general population. A possible explanation for this observation may be a curvilinear dose-response relationship between BMI and postmenopausal BC risk, so that an increased risk may only be observed in populations with a high prevalence of obese/very obese women; (II) tumor characteristics. BMI was significantly associated with tumor size; this applied not only to the cases where the tumor was found by self-detection, but also to lesions detected by radiological breast examinations. In addition, a higher BMI was positively correlated with advanced TNM stage, unfavorable grading and a higher St. Gallen risk score. No associations were observed between BMI and histological subtype, estrogen receptor status, HER2 status and triple negative BC; (III) patient compliance and persistence towards adjuvant BC therapy. Many studies found that the prognosis of overweight/obese BC patients was significantly lower than that of normal weight patients. However, failure of compliance and persistence towards therapy on the part of the patient is not a contributing factor for this observed unfavorable prognosis. In most therapy modes, patients with increasing BMI demonstrated greater motivation and perseverance towards the recommended treatment.

Bone metastases in breast cancer: Frequency, metastatic pattern and non-systemic locoregional therapy.

BACKGROUND: The study evaluates the frequency of and indications for bone-metastases (BM)-related surgery and/or radiotherapy in the palliative breast cancer (BC) situation and analyzes in which phase of the palliative disease course surgery and/or radiotherapy was applied. METHODS: 340 patients who developed distant metastatic disease (DMD) and died (i.e. patients with completed disease courses) were analyzed. RESULTS: From the entire study cohort, 237 patients (69.7%) were diagnosed with BM. Out of these, 116 patients (48.9%) received BM-related radiotherapy and/or surgery during the palliative situation. RADIOTHERAPY: 108 patients (45.6%) received 161 series (range: 1-5) with 217 volumina (range: 1-8) on 300 osseous sites. At 75.3% of the radiated sites, the spine was the most frequent radiated location. Eighty-eight series (54.7%) were performed in the first third of the metastatic disease survival (MDS) period. The median survival after radiotherapy was 14 months (range: 0.2-121 months). SURGERY: In 37 patients (15.6%), 50 procedures (range: 1-4) were necessary to stabilize BM. The femur predominated with 56.0% of the procedures. Twenty procedures (40.0%) were performed in the first third of survival follow-up. The median survival after surgery was 13.5 months (range: 0.5-49 months). BC patients with BM had a significantly improved MDS when radiotherapy and/or surgery for skeletal metastases was embedded in the palliative approach (27.5 months vs. 19.5 months, p<0.001). From the 118 patients who had a MDS of ≥24 months, the majority (54.2%) had BM-related radiotherapy and/or surgery during the palliative course. CONCLUSIONS: Metastatic BC has become increasingly viewed as a chronic disease process. In a general palliative therapy approach, which allows for treatment according to the principles of a chronic disease, non-systemic therapy for BM, in particular radiotherapy, has a clearly established role in the therapy concept.

Impact of breast cancer family history on tumor detection and tumor size in women newly-diagnosed with invasive breast cancer.

This study evaluated the impact of family history (FH) on tumor detection, the patient's age and tumor size at diagnosis in breast cancer (BC). Furthermore, we investigated whether the impact of FH on these features was dependent on degree of relationship, number of relatives with a BC history, or the age of the affected relative at the time that her BC was diagnosed. Out of the entire cohort (n = 1,037), 244 patients (23.5%) had a positive FH; 159 (15.3%) had first-degree relatives affected with BC and 85 patients (8.2%) had second-degree affected relatives. Compared to women who had no BC-affected relatives, the tumors of women who had positive FH were more often found by radiological breast examination (RBE: 31.7%/27.2%, p = 0.008), and they were smaller (general tumor size: 21.8 mm/26.4 mm, p = 0.003; size of tumors found by breast self-examination (BSE): 26.1 mm/30.6 mm, p = 0.041). However, this positive effect of increased use of BC screening and smaller tumor sizes was only observed in patients whose first-degree relatives were affected (comparison with second-degree affected relatives: RBE: 43.8%/24.7%; odds ratio 2.38, p = 0.007; general tumor size: 19.3 mm/26.3 mm; mean difference (MD) -6.9, p = 0.025; tumor size found by BSE: 22.5 mm/31.0 mm; MD -8.5, p = 0.044). When more second-degree relatives or older relatives were diagnosed with BC, the tumors of these patients were similarly often detected by RBE (relationship: 24.7%/27.2%, p = 0.641; age: 33.7 %/27.2 %, p = 0.177) and had similar tumor sizes (general size: 26.3 mm/26.4 mm, p = 0.960; BSE: 31.0 mm/30.6 mm, p = 0.902) as those of women without a FH. Women with a positive FH generally use mammography screening more often and perceive changes in the breast earlier than women without such history. The increased awareness of BC risk decreases if the relationship is more distant.

Strictly defined familial male breast cancer.

The term "familial male breast cancer" is often misleading, because in the breast cancer families reported in the literature, the vast majority of the patients were women and only a few were men. In this report, we present the rare case of a strictly defined familial male breast cancer (MBC) in which exclusively men were diagnosed with breast cancer. Three of four brothers developed the disease between the age of 46 and 64 years within a period of 21 years whereas all female relatives remained unaffected. The three affected men did not show the typical known clinical and genetic risk factors for MBC. An X-linked recessive inheritance may be possible in these cases. One way to potentially improve the identification of the causes of MBC could be a through a strictly studying families in which the male members were exclusively diagnosed with this malignancy. This approach emphasizes familial MBC as a distinct entity and not only as a variant of female breast cancer.

Breast cancer with non-inflammatory skin involvement: current data on an underreported entity and its problematic classification.

We evaluated 166 breast cancer cases with non-inflammatory skin involvement (NISI), which were classified in the TNM classification as T4b. The distribution of tumour sizes and stages was: < or =3 cm:24.1%, 3.1-5 cm:21.7%, 5.1-10 cm:33.1%, >10 cm:21.1%; stages:I/II:21.0%, III:43.4%, IV:35.6%. To assess the impact of NISI on axillary lymph node involvement (ALNI), we analyzed a sub-group of 50 patients with tumours < or =5 cm and compared them with a matched control group. NISI was found to be associated with increased ALNI (HR, 2.66; 95%CI, 1.59-4.63; p<0.0001). According to the inherent rules of tumour classification, only tumours with similar morphologic extent and prognostic significance should be combined. Since there is a high grade of heterogeneity, this basic tenet is clearly violated regarding breast cancer with NISI. Our proposal is to eliminate these tumours from the T4 category and to classify them simply by size (T1-3). Due to its prognostic significance, NISI should be indicated by an optional descriptor (e.g. S1).