History Of Primary Breast Cancer Research Articles

Overrepresentation of human epidermal growth factor receptor 2 positive- and Luminal B breast cancer metastases in the eyes and orbit

BackgroundBreast cancer is the most common cancer to spread to the choroid and orbit. Depending on a set of prognostic and predictive biomarkers, breast cancer can be divided into at least four distinct subtypes with separate treatment and clinical course.SubjectsThirty-two patients with metastases to the eye and periocular area diagnosed between 2005 and 2020, of which 11 also had primary tumour tissue available. Expression levels of oestrogen- (ER) and progesterone receptors (PR), Human epidermal growth factor receptor 2 (HER2) and the proliferation marker Ki67 were analysed.ResultsTwenty-five of 32 patients (78%) had a history of primary breast cancer, whereas the remaining 7 (22%) presented with metastatic disease. Of available metastases, 83% were positive for ER, 37% for PR, 54% for HER2, and 50% for Ki67. Metastases had significantly lower proportions of PR-positive cells than primary tumours, and the distribution of the Luminal A, Luminal B, HER2 enriched and triple-negative subtypes differed between primary tumours and metastases (P = 0.012): Six of 9 patients with a full set of biomarkers on both primary tumours and metastases switched subtype (67%), and 23 of 32 metastases (77%) were of the Luminal B subtype.ConclusionsNearly 4 in 5 breast cancer metastases in the eyes and orbit are of the Luminal B subtype, and a majority are HER2 positive. The breast cancer subtype frequently switches between primary tumours and metastases. Future studies should evaluate these results in larger cohorts.

Experiences of cognitive training on primary breast cancer survivor's cognitive impairments at work: A longitudinal qualitative study.

Cancer-related cognitive impairment (CRCI) is associated with adverse work-related outcomes in women living with a history of primary breast cancer. We explored the perceived impact of receiving adaptive cognitive training (dual n-back training) or active control training (dual 1-back training) on CRCI. Furthermore, we explored the perceived transfer effects of cognitive training on work-related self-management methods for cognitive impairment and work-related outcomes such as career development. Longitudinal qualitative study. A 'framework' analysis approach was used to analyse semi-structured telephone interviews completed by women with a history of primary breast cancer before training (N=40), one month (N=30) and six months (N=29) post-training. Four main themes were identified: (1) impact of cognitive impairment at work, (2) perceived impact of cognitive training on impaired cognitive function, (3) perceived effects of training on work-related self-management methods for cognitive impairment and (4) perceived impact on women's career development and progression. Compared to baseline, women who received adaptive dual n-back training reported sustained improvement in multiple cognitive domains including memory and attention up to six months post-training when the follow-up interviews were conducted. Perceived improvements in cognitive function were associated with greater self-confidence and better emotional well-being in work. These improvements were found to lower dependency on self-management methods for cognitive impairment and enhance effectiveness as well as prompt career development or progression for many women. Although some findings of a similar nature were reported in the active control dual 1-back training group the perceived effects were more pronounced and consistent in the dual n-back group. Adaptive cognitive training (dual n-back training) improves perceived CRCI experienced by women in the workplace, enhancing their self-confidence and general emotional well-being. These perceived improvements, in turn, can decrease reliance on self-management methods for cognitive impairment and improve work efficiency and contribute to career development and progression.

Improved sensitivity in identification of first recurrences of metastatic breast cancer with a combination of cell and cell-free liquid biopsy analysis.

e13003 Background: Liquid biopsy analysis detecting circulating tumor cells (CTC) or circulating tumor DNA (ctDNA) is a non-invasive approach that may provide clinically actionable information for patients’ (pts) treatment decisions when conventional biopsy is otherwise inaccessible or infeasible. Here we report a liquid biopsy method including CTC characterization & ctDNA alterations in pts symptomatic of first metastatic recurrence with a history of primary breast cancer (BC). Methods: Blood samples from 34 symptomatic BC pts were collected for cell & cell-free DNA analysis before undergoing contemporaneous tissue biopsy & initiating treatment for metastatic BC (MBC). Blood was also collected from 25 blood donors (HD) with no known cancer history. After plasma isolation, nucleated cells were plated, & slides were bio-banked. Immunofluorescent staining & subsequent imaging were performed on replicate slides. CTCs were identified using Epic Sciences digital imaging & machine learning algorithms trained to identify breast cancer cells. Single-cell (sc) isolation for genomic quantification of large-scale transitions (scLST) was used to further characterize individual CTCs. cfDNA from bio-banked plasma was analyzed to detect Class IA alterations in ctDNA. Results: Within this cohort of 34 patients, CTCs & ctDNA alterations were detected in 80% & 58%, respectively while no CTCs & ctDNA were detected in the HD cohort suggesting high specificity (100% & 100%). In this study, 26 pts were confirmed MBC (M1-BC) by tissue biopsy, 3 pts were non-MBC by tissue biopsy but still diagnosed as metastatic (Mx-BC), & 5 pts were confirmed non-MBC (M0-BC). To benchmark the cellular (CTCs & scLST+CTCs) & genomic (ctDNA) individual platforms, we designed thresholds of CTCs > 4, scLST+CTC+, & ctDNA+ that optimally identified M1-BC pts with high specificity (100%, 100%, & 100%) but low sensitivity (46%, 46%, & 50%). CTCs > 4 & scLST+CTC+ cutoffs had low concordance with the presence of ctDNA alterations, suggesting these platforms provide independent & complementary value when identifying MBC. To test this hypothesis, we designed combination models [CTC > 4][ctDNA+] & [scLST+CTC+][ctDNA+] that significantly improved sensitivity (75% & 67%) over individual platforms while maintaining high specificity (100% & 100%) when identifying the first recurrence of metastasis in BC pts. Conclusions: To our knowledge, this is the first report showing the additive & complementary value of models combining cellular & genomic liquid biopsy platforms for the detection of the first MBC recurrence. Our data suggest the clinical utility of combined CTC & ctDNA platforms for the identification of MBC when tissue biopsy is inaccessible or infeasible.

Abstract P2-07-04: Risk of primary and contralateral breast cancer in BRCA1/2 mutation carriers previously affected with ovarian cancer

Abstract Introduction: BRCA1/2 mutation carriers are at increased risk of developing breast cancer (BC) and ovarian cancer (OC). However, for BRCA1/2 mutation carriers previously affected with OC, primary BC (PBC) and contralateral BC (CBC) risks might be lowered due to OC treatment, but data hereon are limited. Accurate BC risk estimates are essential for counseling and optimal decision making on BC surveillance and risk-reducing mastectomy (RRM) after diagnosis of BRCA1/2-associated OC. Methods: From the national HEBON cohort study, we selected female BRCA1/2 mutation carriers born from 1940 and at risk of PBC (n=2019; 1194 BRCA1, 825 BRCA2) or at risk of CBC (n=1276; 839 BRCA1, 437 BRCA2). Eligibility criteria for the PBC risk analyses included no history of PBC and both breasts in situ at DNA testing. For the CBC risk analyses, CBC before DNA testing was not allowed and the contralateral breast had to be unaffected at DNA testing. To estimate the association between OC and BC risk, we used the Fine and Gray regression model, with OC as a time-dependent variable and death as competing risk event. The observation started at the age of DNA testing, age 35, or – for the CBC risk analyses – age at PBC diagnosis, whichever came last. Censoring events were RRM, study closing date (i.e. 2014-12-31), and – for the CBC risk analyses – ipsilateral BC recurrence. All analyses were performed separately for BRCA1 and BRCA2 mutation carriers. Results: For the PBC analyses, we selected 236 BRCA1/2 mutation carriers with OC and 1783 BRCA1/2 mutation carriers without OC (median age at start study 53 and 41 years, respectively). During a mean follow-up (FU) of 5.2 years, 15 (6%) OC patients developed PBC after OC, while PBC was diagnosed in 262 (15%) women without OC. OC diagnosis was associated with a lower PBC risk in BRCA1 mutation carriers (HR, 0.27; 95% CI, 0.14–0.53) but not in BRCA2 mutation carriers (HR, 0.88; 95% CI, 0.34–2.27). The cumulative PBC incidence at age 70 in BRCA1 mutation carriers was 25% for OC patients and 66% for women without OC, and in BRCA2 mutation carriers 49% for OC patients and 53% for women without OC. For the CBC analyses, we selected 99 BRCA1/2 mutation carriers affected with PBC and OC, and 1177 BRCA1/2-associated PBC patients without OC (median age at start study 54 and 46 years, respectively). During a mean FU of 3.5 years, 8 (8%) PBC/OC patients developed CBC after OC, while CBC was diagnosed in 131 (11%) PBC patients without OC. In BRCA1 mutation carriers, OC diagnosis was non-significantly associated with a lower CBC risk (HR, 0.44; 95% CI, 0.19–1.03). For BRCA2 mutation carriers the HR was 1.65 (95% CI, 0.34–8.04). The cumulative CBC incidence at age 70 in BRCA1 mutation carriers was 40% for OC patients and 68% for patients without OC; for BRCA2 mutation carriers the number of CBCs was too small to obtain meaningful estimates. Conclusion:­ For BRCA1 mutation carriers affected with OC the risk of developing subsequent BC is lower than for BRCA1 mutation carriers without OC. Our data suggest that the current BC prevention strategies should be reconsidered for OC patients carrying a BRCA1 mutation, possibly including less intensive BC surveillance, and RRM being indicated only for a subgroup of OC patients. Citation Format: Heemskerk-Gerritsen BAM, Hooning MJ, van Doorn HC, Collée MJ, Koppert LB, Jager A, van den Ouweland AMW, Netherlands H, Seynaeve C, Kriege M. Risk of primary and contralateral breast cancer in BRCA1/2 mutation carriers previously affected with ovarian cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-04.

A joint model for multistate disease processes and random informative observation times, with applications to electronic medical records data.

Multistate models are used to characterize individuals' natural histories through diseases with discrete states. Observational data resources based on electronic medical records pose new opportunities for studying such diseases. However, these data consist of observations of the process at discrete sampling times, which may either be pre-scheduled and non-informative, or symptom-driven and informative about an individual's underlying disease status. We have developed a novel joint observation and disease transition model for this setting. The disease process is modeled according to a latent continuous-time Markov chain; and the observation process, according to a Markov-modulated Poisson process with observation rates that depend on the individual's underlying disease status. The disease process is observed at a combination of informative and non-informative sampling times, with possible misclassification error. We demonstrate that the model is computationally tractable and devise an expectation-maximization algorithm for parameter estimation. Using simulated data, we show how estimates from our joint observation and disease transition model lead to less biased and more precise estimates of the disease rate parameters. We apply the model to a study of secondary breast cancer events, utilizing mammography and biopsy records from a sample of women with a history of primary breast cancer.

Improved overall survival after contralateral risk-reducing mastectomy in BRCA1/2 mutation carriers with a history of unilateral breast cancer: a prospective analysis.

Data on survival of BRCA1/2-associated primary breast cancer (PBC) patients who opt for subsequent contralateral risk-reducing mastectomy (CRRM) are scarce and inconsistent. We examined the efficacy of CRRM on overall survival in mutation carriers with a history of PBC. From a Dutch multicentre cohort, we selected 583 BRCA-associated PBC patients, being diagnosed between 1980 and 2011. Over time, 242 patients (42%) underwent CRRM and 341 patients (58%) remained under surveillance. Survival analyses were performed using Cox models, with CRRM as a time-dependent covariate. The median follow-up after PBC diagnosis was 11.4 years. In the CRRM group, four patients developed contralateral breast cancer (2%), against 64 patients (19%) in the surveillance group (p < 0.001). The mortality was lower in the CRRM group than in the surveillance group (9.6 and 21.6 per 1000 person-years of observation, respectively; adjusted hazard ratio 0.49, 95% confidence interval 0.29-0.82). Survival benefit was especially seen in young PBC patients (<40 years), in patients having a PBC with differentiation grade 1/2 and/or no triple-negative phenotype, and in patients not treated with adjuvant chemotherapy. We conclude that CRRM is associated with improved overall survival in BRCA1/2 mutation carriers with a history of PBC. Further research is warranted to develop a model based on age at diagnosis and tumour and treatment characteristics that can predict survival benefit for specific subgroups of patients, aiming at further personalized counselling and improved decision making.

Metastatic renal cell carcinoma presenting as a breast mass in a woman with history of primary breast cancer

Metastatic extramammary breast tumours are uncommon and differential diagnosis with primary breast carcinoma may prove to be difficult. We report a case of a metastasis of a renal cell cancer in the breast in a woman with a history of primary breast cancer. On follow-up of her breast carcinoma, a lump was detected via mammography and ultrasound. Core needle biopsy revealed a metastatic extramammary lesion originating from an asymptomatic renal cell carcinoma. We conclude that the diagnosis of metastasis to the breast from extramammary tumours is important to avoid unnecessary surgery and insure proper treatment of the primary disease.

Randomized Trial of a Hypnosis Intervention for Treatment of Hot Flashes Among Breast Cancer Survivors

Hot flashes are a significant problem for many breast cancer survivors. Hot flashes can cause discomfort, disrupted sleep, anxiety, and decreased quality of life. A well-tolerated and effective mind-body treatment for hot flashes would be of great value. On the basis of previous case studies, this study was developed to evaluate the effect of a hypnosis intervention for hot flashes. Sixty female breast cancer survivors with hot flashes were randomly assigned to receive hypnosis intervention (five weekly sessions) or no treatment. Eligible patients had to have a history of primary breast cancer without evidence of detectable disease and 14 or more weekly hot flashes for at least 1 month. The major outcome measure was a bivariate construct that represented hot flash frequency and hot flash score, which was analyzed by a classic sums and differences comparison. Secondary outcome measures were self-reports of interference of hot flashes on daily activities. Fifty-one randomly assigned women completed the study. By the end of the treatment period, hot flash scores (frequency x average severity) decreased 68% from baseline to end point in the hypnosis arm (P < .001). Significant improvements in self-reported anxiety, depression, interference of hot flashes on daily activities, and sleep were observed for patients who received the hypnosis intervention (P < .005) in comparison to the no treatment control group. Hypnosis appears to reduce perceived hot flashes in breast cancer survivors and may have additional benefits such as reduced anxiety and depression, and improved sleep.

Abdominal Carcinomatosis in Women with a History of Breast Cancer

This paper presents a retrospective review of patients with a history of primary breast cancer who underwent subsequent treatment for abdominal carcinomatosis at the authors' institution from 1988 through 2002. Inclusion criteria included diagnosis of recurrent breast cancer or breast cancer with a second primary cancer, clinical documentation of initial breast cancer, stage of disease, and histologic findings, and laparotomy or laparoscopy with pathologic documentation of abdominal carcinomatosis. The primary breast cancer was retrospectively staged according to the criteria established by the American Joint Committee on Cancer. During the study period, 1501 women were identified who were treated for recurrent breast cancer. Of these, 79 met the study criteria. Patients had an average age of 50 years, and slightly less than half (47%) were postmenopausal. Sixty-two percent of the patients had stage I breast cancer, 21.5% were stage II, 13.9% were stage III, and 2.5% were stage IV. Most women (81%) were diagnosed with infiltrating ductal carcinoma, and 15% had lobular carcinoma. Eighteen of the 79 patients had a previous, nonabdominal, breast cancer recurrence. The median time between diagnosis of breast cancer and surgery for abdominal carcinomatosis was 5.39 years (range, 0.10-33.55 years; mean, 8.37 years). Most women (81%) with abdominal carcinomatosis were postmenopausal. Of the 79 women with abdominal carcinomatosis, 54 (68.4%) were diagnosed with primary ovarian cancer, and 5 (6.3%) were diagnosed with primary peritoneal cancer. The FIGO stage distribution in these 59 patients was stage IIIB in 7 (11.9%), stage IIIC in 41 (69.5%), and stage IV in 11 (18.6%). One woman had a granulose cell tumor; the rest were epithelial tumors. Almost half (49%) of these women had a family history of breast cancer and 8 (13.6%) had a family history of ovarian cancer. Recurrent breast cancer was diagnosed in 19 (24%) of the 79 patients with abdominal carcinomatosis. Although 52.6% had a family history of breast cancer, none of the women with recurrent breast cancer had a family history of ovarian cancer. In a multivariate logistic analysis of variables associated with abdominal carcinomatosis resulting from primary ovarian or peritoneal cancer, stage I breast cancer, and the absence of a prior breast cancer recurrence were significantly more likely to be predictive of primary ovarian/peritoneal cancer than recurrent breast cancer (odds ratio [OR] = 10.73, 95% confidence interval [CI] = 2.6-43.7; and OR = 10.60, 95% CI = 2.5-45.2, respectively; P = 0.001 for both). A strong but nonsignificant association with primary ovarian/peritoneal cancer versus recurrent breast cancer was seen for longer interval between diagnosis of breast cancer and diagnosis of abdominal carcinomatosis and higher levels of serum CA-125. Most patients underwent exploratory laparotomy with bilateral salpingo-oophorectomy (n = 68), hysterectomy (n = 54), and various degrees of tumor cytoreduction, although 9 patients underwent only diagnostic laparoscopy with biopsies. Optimal cytoreduction, that is, the maximal diameter of the largest residual tumor mass was 1 cm or less, was performed in 33 (55.9%) patients. Over 90% of patients received a platinum-based chemotherapy alone or in combination with other agents. After a median follow up of 51.6 months, the median survival for these patients was 30 months. In 19 of the 33 patients with optimal cytoreduction, 18 had no visible residual disease. The median survival time for these patients was 82 months compared with 33 months for optimally reduced patients with some visible disease (hazard ratio [HR] = 10.07, 95% CI = 3.34-31.26, P < 0.0001), and 18 months for patients with suboptimal cytoreduction (HR = 26.37,95% CI = 8.30-83.74, P < 0.0001). At the last follow up, 10 patients, all of whom had no visible residual disease, were alive after more than 5 years. In the women with a final diagnosis of metastatic breast cance

Contralateral Breast Cancer and Thromboembolic Events in African American Women Treated With Tamoxifen

Information about breast cancer treatment and prevention in African American women is scant, and recommendations for therapy from clinical trials for breast cancer are based primarily on data obtained from white women. We compared the effects of tamoxifen on risk of contralateral breast cancer and thromboembolic events in African American women and white women with a history of primary breast cancer. Data from 13 National Surgical Adjuvant Breast and Bowel Project clinical trials were pooled for analyses of time to contralateral breast cancer as a first event (eight trials and 10,619 patients) and of time to any thromboembolic phenomenon as a first event (all 13 trials and 20,878 patients). Risk factors for contralateral breast cancer and thromboembolic events among all women were determined using univariate proportional hazards models. (For each racial group, the rate of events associated with tamoxifen use was calculated as the ratio of the incidence rate with tamoxifen to that without tamoxifen.) Proportional hazards regression models were used to calculate 95% confidence intervals (CIs) and risk ratios. All statistical tests were two-sided. Risk factors for contralateral breast cancer were body mass index (BMI) and lymph node positivity; those for thromboembolic events were BMI and age. In women of both ethnicities with estrogen receptor-positive breast cancer, those who took tamoxifen experienced a similar reduction in contralateral breast cancer (risk ratio for African American women = 0.74, 95% CI = 0.46 to 1.17, n = 690; risk ratio for white women = 0.76, 95% CI = 0.59 to 0.98, n = 9929; P = .92). Tamoxifen was also associated with an increase in thromboembolic events. The relative risk for thromboembolic events was higher in both African American and white women treated with tamoxifen and chemotherapy than in those who were treated with tamoxifen alone (risk ratio for African American women = 10.70, 95% CI = 5.94 to 19.28 versus 2.16, 95% CI = 1.26 to 3.71; n = 1842; risk ratio for white women = 15.49, 95% CI = 9.53 to 25.17 versus 3.13, 95% CI = 2.04 to 4.79, n = 19,036), and this effect was similar between the races (P = .10). African American and white women appear to have the same risks of contralateral breast cancer and thromboembolic events in response to tamoxifen treatment.

Radical Resection of Radiation-Induced Sarcoma of the Chest Wall: Report of 15 Cases

Background. Surgical management of radiation-induced sarcoma of the chest wall remains difficult because of its impressive local aggressiveness. Methods. Between 1987 and 1995, 15 patients (median age, 58 years) underwent radical resection of radiation-induced sarcoma of the chest wall. This type of tumor was defined as a metachronous, histologically different neoplasm in the irradiated field of the original tumor. Ten patients had a history of primary breast cancer and 5 patients, Hodgkin’s disease. The median delivered radiation dose to the primary tumor area was 45 Gy, and the median interval between radiotherapy and diagnosis of sarcoma was 14 years. Seven tumors were located on the sternum, three on the lateral chest wall, and five in the thoracic outlet. Four total and three partial sternectomies, three lateral chest wall resections and five resections of tumors in the thoracic outlet (three first-rib resections) were performed. Seven patients required stabilization of the chest wall with prosthetic material. Soft tissue reconstruction was carried out with either muscle flaps and skin advancement in 9, musculocutaneous flaps in 4, or skin flaps alone in 2 patients. Results. One patient died 3 months after total sternectomy of respiratory failure. Two patients (13.3%) had a local complication: sepsis after sternectomy in 1 and cutaneous necrosis in 1. Local recurrence occurred in 7 patients after a median interval of 10 months. Two of them died, and 4 underwent a repeat resection, 3 of whom are still alive. Four patients died of systemic recurrence. With a median follow-up of 30 months, overall 5-year survival and 5-year disease-free survival rates were 48% and 27%, respectively. Conclusion. Despite poor long-term disease-free survival, radical resection of radiation-induced sarcoma of the chest wall is justified on the basis of low postoperative morbidity and the lack of other available therapies. (Ann Thorac Surg 1997;63:214–9)