ABSTRACT
PURPOSE: In patients with a biopsy-proven ductal carcinoma in situ (DCIS), axillary staging is frequently performed, but in hindsight often turns out to be superfluous. The aim of this observational study was to develop a prediction model for risk of lymph node metastasis in patients with a biopsy-proven DCIS. METHODS: Data were received from the Dutch Pathology Databank and the Netherlands Cancer Registry. The population-based cohort consisted of all biopsy-proven DCIS patients diagnosed in the Netherlands in 2011 and 2012. The prediction model was evaluated with the area under the curve (AUC) of the receiver operating characteristic, and a calibration plot and a decision curve analysis and was validated in a Dutch cohort of patients diagnosed in the period 2016-2019. RESULTS: Of 2892 biopsy-proven DCIS patients, 127 had metastasis (4.4%). Risk factors were younger age (OR = 0.97, 95% CI 0.95-0.99), DCIS not detected by screening (OR = 1.55, 95% CI 1.01-2.38), suspected invasive component at biopsy (OR = 1.86, 95% CI 1.01-3.41), palpable tumour (OR = 2.06, 95% CI 1.34-3.18), BI-RADS score 5 (OR = 2.41, 95% CI 1.53-3.78), intermediate-grade DCIS (OR = 3.01, 95% CI 1.27-7.15) and high-grade DCIS (OR = 3.20, 95% CI 1.36-7.54). For 24% (n = 708) of the patients, the predicted risk of lymph node metastasis was above 5%. Based on the decision curve analysis, the model had a net benefit for a predicted risk below 25%. The AUC was 0.745. Of the 2269 patients in the validation cohort, 53 (2.2%) had metastasis and the AUC was 0.741. CONCLUSIONS: This DCIS-met model can support clinical decisions on axillary staging in patients with biopsy-proven DCIS.
Subject(s)
Breast Neoplasms , Carcinoma, Ductal, Breast , Carcinoma, Intraductal, Noninfiltrating , Humans , Female , Carcinoma, Intraductal, Noninfiltrating/surgery , Carcinoma, Intraductal, Noninfiltrating/pathology , Lymphatic Metastasis , Biopsy , Breast/pathology , Carcinoma, Ductal, Breast/pathology , Axilla/pathology , Breast Neoplasms/surgery , Sentinel Lymph Node Biopsy , Retrospective StudiesABSTRACT
BACKGROUND: This study aimed to validate the DCIS-upstage model, a previously developed model to predict the risk of upstaging to invasive breast cancer in patients with biopsy-proven ductal carcinoma in situ (DCIS) in a more recent cohort and to assess the model's clinical utility. METHODS: The model was validated in a registry cohort (n = 2269) and in an institution cohort (n = 302). A calibration plot was made, followed by a decision curve analysis (DCA). The model's area under the curve (AUC) was compared with the AUC of another published model and with the AUCs of new models using the risk factors of the DCIS-upstage model and additional risk factors. RESULTS: The DCIS-upstage model had an AUC of 0.67 at development; in the validation, the AUC was 0.65 in the registry cohort and 0.73 in the institution cohort. The DCA showed that the model has clinical utility. The other published model had an AUC of 0.66 in the institution cohort. Adding risk factors to the DCIS-upstage model slightly increased the AUC. CONCLUSIONS: The DCIS-upstage prediction model is valid in other cohorts. The model has clinical utility and may be used to select patients with biopsy-proven DCIS for sentinel lymph node biopsy.
ABSTRACT
The prospective, multicenter TESTBREAST study was initiated with the aim of identifying a novel panel of blood-based protein biomarkers to enable early breast cancer detection for moderate-to-high-risk women. Serum samples were collected every (half) year up until diagnosis. Protein levels were longitudinally measured to determine intrapatient and interpatient variabilities. To this end, protein cluster patterns were evaluated to form a conceptual basis for further clinical analyses. Using a mass spectrometry-based bottom-up proteomics strategy, the protein abundance of 30 samples was analyzed: five sequential serum samples from six high-risk women; three who developed a breast malignancy (cases) and three who did not (controls). Serum samples were chromatographically fractionated and an in-depth serum proteome was acquired. Cluster analyses were applied to indicate differences between and within protein levels in serum samples of individuals. Statistical analyses were performed using ANOVA to select proteins with a high level of clustering. Cluster analyses on 30 serum samples revealed unique patterns of protein clustering for each patient, indicating a greater interpatient than intrapatient variability in protein levels of the longitudinally acquired samples. Moreover, the most distinctive proteins in the cluster analysis were identified. Strong clustering patterns within longitudinal intrapatient samples have demonstrated the importance of identifying small changes in protein levels for individuals over time. This underlines the significance of longitudinal serum measurements, that patients can serve as their own controls, and the relevance of the current study set-up for early detection. The TESTBREAST study will continue its pursuit toward establishing a protein panel for early breast cancer detection.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Proteome/metabolism , Prospective Studies , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Blood Proteins/analysis , Biomarkers , Biomarkers, TumorABSTRACT
OBJECTIVE: Unmet health care needs require additional care resources to achieve optimal patient well-being. In this nationwide study we examined associations between a number of risk factors and unmet needs after treatment among women with breast cancer, while taking into account their health care practices. We expected that more care use would be associated with lower levels of unmet needs. METHODS: A multicenter, prospective, observational design was employed. Women with primary breast cancer completed questionnaires 6 and 15 months post-diagnosis. Medical data were retrieved from medical records. Direct and indirect associations between sociodemographic and clinical risk factors, distress, care use, and unmet needs were investigated with structural equation modeling. RESULTS: Seven hundred forty-six participants completed both questionnaires (response rate 73.7%). The care services received were not negatively associated with the reported levels of unmet needs after treatment. Comorbidity was associated with higher physical and daily living needs. Higher age was associated with higher health system-related and informational needs. Having had chemotherapy and a mastectomy were associated with higher sexuality needs and breast cancer-specific issues, respectively. A higher level of distress was associated with higher levels of unmet need in all domains. CONCLUSIONS: Clinicians may use these results to timely identify which women are at risk of developing specific unmet needs after treatment. Evidence-based, cost-effective (online) interventions that target distress, the most influential risk factor, should be further implemented and disseminated among patients and clinicians.
Subject(s)
Breast Neoplasms/psychology , Cancer Survivors/psychology , Health Services Needs and Demand/statistics & numerical data , Patient Satisfaction/statistics & numerical data , Adult , Aged , Breast Neoplasms/therapy , Female , Humans , Mastectomy/statistics & numerical data , Middle Aged , Needs Assessment/standards , Prospective Studies , Risk Factors , Social Support , Surveys and QuestionnairesABSTRACT
BACKGROUND: The number of women with breast cancer in general practice is rising. To address their needs and wishes for a referral, GPs might benefit from more insight into women's health care practices and need for additional support. OBJECTIVE: To examine the prevalence of health care use and remaining needs among women with breast cancer in the first 15 months after diagnosis. METHODS: In this multicentre, prospective, observational study women with breast cancer completed a questionnaire at 6 and 15 months post-diagnosis. Medical data were retrieved through chart reviews. The prevalence of types of health care used and remaining needs related to medical, psychosocial, paramedical and supplementary service care (such as home care), was examined with descriptive analyses. RESULTS: Seven hundred forty-six women completed both questionnaires. At both assessments patients reported that they had most frequent contact with medical and paramedical providers, independent of types of treatment received. Three to fifteen percent of the patients expressed a need for more support. Prominent needs included a wish for more frequent contact with a physiotherapist, a clinical geneticist and a psychologist. Patients also wanted more help for chores around the house, particularly in the early post-treatment phase. CONCLUSION: A small but relevant percentage of women with breast cancer report having unmet needs. GPs may need to be particularly watchful of their need for more support from specific providers. Future research into the necessity of structural needs assessment among cancer patients in general practice is warranted.
Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , General Practitioners , Health Services Needs and Demand , Patient Acceptance of Health Care , Physician's Role , Social Support , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Needs Assessment , Prospective Studies , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Patients with a biopsy diagnosis of ductal carcinoma in situ (DCIS) might be diagnosed with invasive breast cancer at excision, a phenomenon known as underestimation. Patients with DCIS are treated based on the risk of underestimation or progression to invasive cancer. The aim of our study was to expand the knowledge on underestimation and to develop a prediction model. METHODS: Population-based data were retrieved from the Dutch Pathology Registry and the Netherlands Cancer Registry for DCIS between January 2011 and June 2012. RESULTS: Of 2892 DCIS biopsies, 21% were underestimated invasive breast cancers. In multivariable analysis, risk factors were high-grade DCIS (odds ratio (OR) 1.43, 95% confidence interval (CI): 1.05-1.95), a palpable tumour (OR 2.22, 95% CI: 1.76-2.81), a BI-RADS (Breast Imaging Reporting and Data System) score 5 (OR 2.36, 95% CI: 1.80-3.09) and a suspected invasive component at biopsy (OR 3.84, 95% CI: 2.69-5.46). The predicted risk for underestimation ranged from 9.5 to 80.2%, with a median of 14.7%. Of the 596 invasive cancers, 39% had unfavourable features. CONCLUSIONS: The risk for an underestimated diagnosis of invasive breast cancer after a biopsy diagnosis of DCIS is considerable. With our prediction model, the individual risk of underestimation can be calculated based on routinely available preoperatively known risk factors ( https://www.evidencio.com/models/show/1074 ).
Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Carcinoma, Intraductal, Noninfiltrating/pathology , Models, Theoretical , Adult , Biopsy , Breast Neoplasms/epidemiology , Carcinoma, Intraductal, Noninfiltrating/epidemiology , Disease Progression , Female , Humans , Middle Aged , Neoplasm Invasiveness , Netherlands/epidemiology , Registries , Retrospective Studies , Risk FactorsABSTRACT
To date, little is known about enduring clinical distress as measured with the commonly used distress thermometer. We therefore used the distress thermometer to examine: (a) the prevalence of enduring clinical distress, distress-related problems, and subsequent wish for referral of women with breast cancer, and (b) sociodemographic, clinical, and psychosocial predictors of enduring clinical distress. The study had a multicenter, prospective, observational design. Patients with primary breast cancer completed a questionnaire at 6 and 15 months postdiagnosis. Medical data were retrieved from chart reviews. Enduring clinical distress was defined as heightened distress levels over time. The prevalence of enduring clinical distress, problems, and wish for referral was examined with descriptive analyses. Associations between predictors and enduring clinical distress were examined with multivariate analyses. One hundred sixty-four of 746 patients (22 %) reported having enduring clinical distress at 6 and 15 months postdiagnosis. Of these, 10 % wanted to be referred for care. Fatigue was the most frequently reported problem by patients with and without clinical distress, at both time points. Lack of muscle strength (OR = 1.82, 95 % CI 1.12-2.98), experience of a low level of life satisfaction (OR = 0.77, 95 % CI 0.67-0.89), more frequent cancer worry (OR = 1.40, 95 % CI 1.05-1.89), and neuroticism (OR = 1.09, 95 % CI 1.00-1.18) were predictors of enduring clinical distress. In conclusion, one in five women with breast cancer develops enduring clinical distress. Oncologists, nurse practitioners, and cancer nurses are advised to use single-item questions about distress and distress-related problems to ensure timely detection of high-risk patients. Providers should also routinely assess fatigue and its causes, as fatigue is the most frequently reported distress-related problem over time.
Subject(s)
Breast Neoplasms/surgery , Mastectomy, Segmental/methods , Stress, Psychological/ethnology , Breast Neoplasms/ethnology , Breast Neoplasms/psychology , Cross-Sectional Studies , Female , Humans , Medicaid , Middle Aged , Prospective Studies , Quality of Health Care , Quality of Life , Stress, Psychological/etiology , Surveys and Questionnaires , Time-to-Treatment , United States/ethnologyABSTRACT
BACKGROUND: Breast cancer is a common malignancy, but metastases to the breast of extramammary malignancies are very rare. Treatment and prognosis are different. The aim of the study is to report the incidence of lymphomas and metastases to the breast of extramammary malignancies in our 30-year archive. METHODS: The pathology database of a single institute was reviewed for all breast neoplasms which were coded in our system as a metastasis in the period 1985-2014. Metastatic tumors from primary breast carcinoma were excluded. RESULTS: A total of 47 patients were included (7 men/40 women, mean age 63 years). The majority originated from lymphoma (n = 18) and primary melanoma (n = 11). Other primary tumor sites included the ovary (n = 6), lung (n = 6), colon (n = 3), kidney (n = 1), stomach (n = 1), and chorion (n = 1). In 24/47 patients (51 %), metastasis was the first sign of the specific malignant disease. In seven patients (15 %) surgery was performed, the diagnosis of metastatic disease was adjusted in four patients (9 %) postoperatively. CONCLUSIONS: It is important to distinguish lymphomas and metastases to the breast from common primary breast carcinoma for proper treatment and prognosis. Therefore, we emphasize the need for a histological or cytopathological diagnosis before any treatment is commenced. The pathologist plays a key role in considering the diagnosis of metastasis if the histological features are unusual for a primary breast carcinoma. The pathologist should therefore be properly informed by the clinical physician although lymphomas and metastases to the breast are the first presentation of malignant disease in half the cases.
Subject(s)
Breast Neoplasms/secondary , Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Breast Neoplasms/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Neoplasms/surgery , Prognosis , Retrospective StudiesABSTRACT
BACKGROUND: Prophylactic skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) both are associated with major risk reduction in women with high breast cancer risk. Skin-sparing mastectomy followed by nipple-areola complex (NAC) reconstruction is standard of care, but NSM is increasingly being performed. Preservation of the NAC in NSM may increase patient satisfaction. Therefore, we measured NAC sensitivity after NSM and compared patient satisfaction as well as body image after SSM with NSM. METHODS: Women who underwent prophylactic bilateral SSM or NSM and immediate implant breast reconstruction between 2002 and 2012 were eligible. Patient satisfaction was assessed using the Breast-Q reconstruction questionnaire, body image using Hopwood's body image scale (BIS), and satisfaction with the (reconstructed) NAC using a study-specific questionnaire. In the NSM group, NAC sensitivity was assessed using Semmes Weinstein monofilaments with a 5-point scale and compared with NAC sensitivity in a nonoperated control group. RESULTS: The SSM group comprised 25 women (50 SSMs) and the NSM group 20 women (39 NSMs). Median follow-up was 65 months in the SSM group compared with 27 months in the NSM group (P < 0.01). In univariable analyses, Breast-Q scores were favorable in the SSM group compared with the NSM group with trends for higher "satisfaction with breasts" (66.2 vs 56.6; P = 0.06) and "satisfaction with outcome" (76.1 vs 61.5; P = 0.09). Mean BIS score of 7.1/30 in the SSM group and 9.3/30 in the NSM group (P = 0.35). Adjusted for follow-up, there were no significant differences in Breast-Q scores, nor in BIS scores. Interestingly, satisfaction with the (reconstructed) NAC was similar after SSM and NSM. Nipple-areola complex sensitivity was lower in the NSM group (mean score, 1.9; 95% confidence interval, 1.5-2.3) compared with the control group (mean score, 4.7; 95% confidence interval, 4.6-4.9; P < 0.01). CONCLUSIONS: Breast-Q scores regarding satisfaction with breasts and overall outcome were in favor of the SSM group. Residual NAC sensitivity after NSM was low. This suggests that SSM followed by NAC reconstruction is a balanced alternative to NSM. We observed no significant differences in body image and NAC-specific satisfaction between the NSM and SSM groups.
Subject(s)
Breast Implantation/methods , Breast Neoplasms/prevention & control , Mastectomy, Subcutaneous/methods , Nipples/surgery , Patient Satisfaction/statistics & numerical data , Prophylactic Mastectomy/methods , Touch , Adult , Body Image , Case-Control Studies , Female , Follow-Up Studies , Humans , Nipples/physiology , Patient Reported Outcome Measures , Retrospective StudiesABSTRACT
BACKGROUND: Preoperative objective predictions of cosmetic result after breast conserving surgery (BCS) has the potential to aid in surgical treatment decision making. Our aim was to investigate the predictive value of tumor volume in relation to breast volume (TV/BV ratio) for cosmetic result. METHODS: Sixty-nine invasive breast cancer women with preoperative MRI and treated by BCS and radiotherapy in 2007-2012 were prospectively included. Simple excision or basic oncoplastic techniques were used, but no volume displacement. TV/BV ratio was measured in the MRI while 3D-projected in virtual reality environment (I-Space). Cosmetic result was assessed by patient questionnaire, panel evaluation, and breast retraction assessment (BRA). Quality-of-life was assessed by EORTC QLQ-C30 and BR23. RESULTS: Intraobserver and interobserver correlation coefficients for tumor and breast volume were all >0.95. Increasing TV/BV ratio correlated with decreasing cosmetic result as determined by patient, panel, and BRA. TV/BV ratio was a significant independent predictor for the panel evaluation (P=0.028), as was tumor location (P<0.05), and together they constituted a good prediction model (AUC 0.83). CONCLUSIONS: TV/BV ratio was a precise and independent predictor for cosmetic result determined by a panel and can be used as preoperative prediction tool to enable more informed surgical treatment decision making.
Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/surgery , Esthetics , Mastectomy, Segmental , Aged , Breast/pathology , Breast Neoplasms/radiotherapy , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/radiotherapy , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/pathology , Carcinoma, Lobular/radiotherapy , Carcinoma, Lobular/surgery , Female , Humans , Middle Aged , Preoperative Period , Prospective Studies , Quality of Life , Tumor BurdenABSTRACT
BACKGROUND: Some women at risk for hereditary breast cancer are at increased risk of psychological distress. In order to tailor support for individual women, the availability of a tool enabling the identification of psychologically vulnerable women at an early stage is warranted. The objectives of this study were (1) to explore long-term psychological distress in women at risk for hereditary breast cancer adhering to regular surveillance, and (2) to identify women being vulnerable for long-term psychological distress, defined in terms of a multifactorial risk profile. METHODS: General distress and cancer-related distress were assessed at baseline (T0) and after 5-8 years (T1) in 197 high-risk women adhering to breast cancer surveillance. Coping styles, occurrence of breast cancer in the family of origin, breast cancer risk perception, and frequency of breast self-examination, as assessed at T0, were examined as predictor variables for long-term distress (T1). RESULTS: Across time, women reported a significant reduction in intrusion and avoidance. Intrusion levels were increased among women who had lost a first-degree relative to breast cancer. Predictors of increased long-term distress were passive and palliative coping styles, excessive breast self-examination, and overestimation of breast cancer risk. On the other hand, coping through fostering reassuring thoughts was predictive for decreased long-term distress. CONCLUSION: On the basis of the identified risk profile, it is possible to identify vulnerable women at an early stage, who then may be offered additional and individually tailored support.
Subject(s)
Breast Neoplasms/psychology , Genetic Predisposition to Disease/psychology , Hereditary Breast and Ovarian Cancer Syndrome/psychology , Stress, Psychological/psychology , Adaptation, Psychological , Adult , Aftercare/psychology , Breast Neoplasms/diagnosis , Breast Self-Examination/psychology , Breast Self-Examination/statistics & numerical data , Female , Follow-Up Studies , Humans , Middle Aged , Risk AssessmentABSTRACT
BACKGROUND: Previously published studies report up to 30% recurrence rates after DCIS, so it would be desirable to identify those women at risk for recurrence and adapt adjuvant management. This study aimed to identify the locoregional recurrence rate after breast conserving surgery (BCS) for DCIS, and to evaluate the possible role of immunohistochemical (IHC) staining in predicting the risk of recurrence. PATIENTS AND METHODS: In a retrospective cohort study, patients who underwent BCS for pure DCIS were identified. Data on well-established clinical-pathological risk factors and development of locoregional recurrence was gathered from patient files. In addition, IHC stains of ER, PR, HER2, p53, and ki67 were performed on original tumor samples. Univariable Cox regression analyses were performed to identify possible risk factors for locoregional recurrence. RESULTS: 190 patients were included. At a median follow-up time of 12.8 years fifteen (8%) patients developed locoregional recurrence: 7 invasive cancer and 8 DCIS. These recurrences were diagnosed within a range of 1.7 to 19.6 years after the initial diagnosis. Univariable Cox regression analysis did only show a significant association between p53 and locoregional recurrence. Our re-excision rate to obtain free margins was 30.5%, and 90% received radiotherapy. Endocrine treatment was not used. CONCLUSIONS: At 12.8 years follow-up, patients with DCIS treated with BCS have a very low locoregional recurrence of 8%. Although we could demonstrate that increased p53 expression is a risk factor for locoregional recurrence, we think this is of little clinical value in our population with such a low recurrence rate. MICROABSTRACT: With a published recurrence rate up to 30% after DCIS, it would be desirable to identify those at risk to adapt treatment and follow-up. We aimed to evaluate the role of immunohistochemical staining to determine the risk of locoregional recurrence, in addition to established clinical and pathological risk factors. At a median follow-up of 12.8 years, we found a locoregional recurrence rate of 8%. Increased expression of p53 is associated with an increased risk of locoregional recurrence.
Subject(s)
Breast Neoplasms , Carcinoma, Intraductal, Noninfiltrating , Humans , Female , Mastectomy, Segmental , Carcinoma, Intraductal, Noninfiltrating/surgery , Carcinoma, Intraductal, Noninfiltrating/pathology , Retrospective Studies , Tumor Suppressor Protein p53 , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/surgery , Breast Neoplasms/surgeryABSTRACT
PURPOSE: To establish the breast reconstruction rate in a large Dutch teaching hospital, and to gain insight into the motives of women to opt for or reject post-mastectomy breast reconstruction. METHODS: In a retrospective, cross-sectional study, all consecutive patients who underwent mastectomy for invasive breast cancer or ductal carcinoma in situ (DCIS) were identified and categorized into two groups based on subsequent breast reconstruction or not. Patient-reported outcomes were assessed with the validated Breast-Q and a short survey about the decision-making process in breast reconstruction. These outcomes were compared between the two groups using univariable analyses, multivariable logistic regression, and multiple linear regression analyses. The Breast-Q scores were also compared to Dutch normative values. RESULTS: A total of 319 patients were identified of whom 68% had no breast reconstruction. Of the 102 patients with breast reconstruction, the majority (93%) received immediate, instead of delayed breast reconstruction. The survey was completed by 155 (49%) patients. The non-reconstruction group, on average, reported significantly poorer psychosocial well-being, compared to the reconstruction group as well as compared to the normative data. However, the majority of the non-reconstruction group (83%) stated that they had no desire for breast reconstruction. In both groups, most patients stated that the provided information was sufficient. CONCLUSION: Patients have personal motives to opt for or reject breast reconstruction. It seemed that patients differ in their rating of values that affect their decision since the same arguments were used to opt for or reject reconstruction. Notably, patients were well-informed in their decision making.
Subject(s)
Breast Neoplasms , Mammaplasty , Humans , Female , Breast Neoplasms/pathology , Mastectomy/psychology , Cross-Sectional Studies , Retrospective StudiesABSTRACT
BACKGROUND: We assessed the efficacy of taxane chemotherapy in BRCA1- and BRCA2-associated patients compared with sporadic metastatic breast cancer patients. METHODS: Response rates (RRs) to and progression-free survival (PFS) after taxane chemotherapy of 35 BRCA1-associated and 13 BRCA2-associated metastatic breast cancer patients were compared with those outcomes in 95 matched (1:2) sporadic patients. Matching was performed for age at and year of diagnosis of primary breast cancer, year of metastatic disease, and line of therapy (first vs second or third). RESULTS: Among BRCA1-associated patients, the RR was worse (objective response [OR], 23% vs 38%; progressive disease [PD], 60% vs 19%; P < 0.001); and the median PFS shorter (2.2 vs 4.9 months; P = 0.04) compared with sporadic patients. In the subgroup of hormone receptor (HRec)-negative patients, BRCA1-associated patients (n = 20) had a worse RR (OR, 20% vs 42%, respectively; PD, 70% vs 26%, respectively; P = 0.03) and a shorter PFS (1.8 vs 3.8 months; P = 0.004) compared with sporadic patients (n = 19). These outcomes in HRec-positive patients were similar in BRCA1-associated (n = 11) and sporadic (n = 61) patients (OR, 36% vs 38%; PD, 28% vs 20%; median PFS, both 5.7 months). In BRCA2-associated patients, who were mainly HRec-positive, the OR was higher than in sporadic patients (89% vs 38%, respectively; P = 0.02), whereas the median PFS was not significantly different (7.1 vs 5.7 months, respectively). CONCLUSIONS: BRCA1-associated, HRec-negative metastatic breast cancer patients were less sensitive to taxane chemotherapy than sporadic HRec-negative patients. HRec-positive BRCA1- and BRCA2-associated patients had a sensitivity to taxane chemotherapy similar to that of sporadic patients.
Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/secondary , Bridged-Ring Compounds/therapeutic use , Mutation/genetics , Taxoids/therapeutic use , Adult , Antineoplastic Agents/therapeutic use , Breast Neoplasms/genetics , Case-Control Studies , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic , Genetic Testing , Humans , Middle Aged , Pharmacogenetics , Prognosis , Receptors, Estrogen/genetics , Receptors, Progesterone/genetics , Retrospective Studies , Treatment OutcomeABSTRACT
Global gene expression profiling studies have classified breast cancer into molecular classes, some of which show similarity to normal mammary cells (ie luminal and basal subtypes) with a subsequent histogenetic implication that reinforced the perception that the phenotype of breast cancer reflects the cell of origin. However, it remains to be determined whether phenotypic changes are the result of malignant transformation of particular cancer stem cells (histogenesis) or specific genetic hits occurring at various stages of carcinogenesis (dedifferentiation). We sought to test the hypothesis that dedifferentiation may be the more likely explanation using in vivo clinical data. Our findings support the hypothesis that at least some metaplastic carcinomas are derived from phenotypic transition from conventional mammary adenocarcinoma either at the in-situ, primary invasive stage or at a distant metastatic site. This observation argues against the cell of origin theory (histogenesis) for breast carcinogenesis and favours the concept of tumour dedifferentiation at later stages.
Subject(s)
Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Cell Dedifferentiation , Female , Humans , Metaplasia/pathology , Neoplasm Invasiveness , Neoplastic Stem Cells/pathologyABSTRACT
Gastric metastasis of breast cancer is a known mimicker of primary gastric cancer. This paper demonstrates that in patients with a history of breast cancer, gastric metastasis and primary gastric cancer are equally likely.
ABSTRACT
BACKGROUND: There is a large variation between Dutch hospitals in the use of Sentinel Lymph Node Biopsy (SLNB) in patients with a biopsy diagnosis of Ductal Carcinoma in Situ. The aim of our study was to investigate whether this variation might be explained by preferences of surgeons, organisational factors or the influence of patients preferences. METHODS: A cross-sectional web survey was conducted among 260 Dutch oncological/breast surgeons. Preferences of surgeons and the influence of the patients' preferences were determined by means of best-worst scaling (BWS) of profile case scenarios and by ranking risk factors. The survey also explored organisational questions, the reported use of diagnostic techniques and influences on the decision. RESULTS: The BWS scenarios were completed by 57 surgeons. The most important reasons for performing SLNB were a suspected invasive component and DCIS grade 3. In the ranking, these were also the first and second most important factor, followed by the size of the lesion and a mass on mammogram. In 58% to 70% of the scenarios, the surgeons would not change their decisions on the use of SLNB if the patient's chose differed. No organisational factor was significantly associated with the reported use of SLNB. CONCLUSION: The inter-hospital variation in the use of SLNB could not be attributed to organisational factors or surgeons' preferences for risk factors. The risk factors that most surgeons reported as reasons for performing SLNB are consistent with the factors described in the Dutch treatment guideline for the use of SLNB.