Mode of Detection of Second Breast Cancers in Patients Undergoing Surveillance After Treatment of Ductal Carcinoma in Situ.

BACKGROUND: For patients undergoing posttreatment surveillance after ductal carcinoma in situ (DCIS), the NCCN Guidelines for Breast Cancer recommend annual breast imaging and physical examination every 6 to 12 months for 5 years, and then annually. The aim of our study was to evaluate the modes of detection (imaging, patient reported, or physical examination) of second cancers in a cohort of patients undergoing surveillance after primary DCIS treatment to better inform surveillance recommendations. METHODS: We performed a retrospective cohort study of patients with DCIS treated between January 1, 2008, and December 31, 2011, within a large integrated health care system. Information on patient demographics, index DCIS treatment, tumor characteristics, and mode of detection of second breast cancer was obtained from the electronic health record or chart review. RESULTS: Our study cohort consisted of 1,550 women, with a median age of 59 years at diagnosis. Surgical treatment of DCIS included lumpectomy (75.0%; n=1,162), unilateral mastectomy (21.1%; n=327), or bilateral mastectomy (3.9%; n=61), with or without sentinel lymph node biopsy. Additionally, 44.4% (n=688) and 28.3% (n=438) received radiation and endocrine therapies, respectively. Median follow-up was 10 years, during which 179 (11.5%) women were diagnosed with a second breast cancer. Of the second cancers, 43.0% (n=77) were ipsilateral and 54.8% (n=98) contralateral, and 2.2% (n=4) presented with distant metastases; 61.5% (n=110) were invasive, 36.3% (n=65) were DCIS, and 2.2% (n=4) were Paget's disease. Second breast cancers were imaging-detected in 74.3% (n=133) of cases, patient-detected in 20.1% (n=36), physician-detected in 2.2% (n=4), and detected incidentally on imaging or pathology from procedures unrelated to oncologic care in 3.4% (n=6). CONCLUSIONS: In our cohort of patients undergoing surveillance following diagnosis and treatment of DCIS, 2% of second breast cancers were detected by a clinical breast examination. This suggests that survivorship care should prioritize mammography and patient education regarding breast self-examination and symptoms that warrant evaluation to detect second breast cancers.

Active surveillance versus treatment in low-risk DCIS: Women's preferences in the LORD-trial.

BACKGROUND: Ductal carcinoma in situ (DCIS) can progress to invasive breast cancer (IBC), but most DCIS lesions remain indolent. However, guidelines recommend surgery, often supplemented by radiotherapy. This implies overtreatment of indolent DCIS. The non-randomised patient preference LORD-trial tests whether active surveillance (AS) for low-risk DCIS is safe, by giving women with low-risk DCIS a choice between AS and conventional treatment (CT). Here, we aim to describe how participants are distributed among both trial arms, identify their motives for their preference, and assess factors associated with their choice. METHODS: Data were extracted from baseline questionnaires. Descriptive statistics were used to assess the distribution and characteristics of participants; thematic analyses to extract self-reported reasons for the choice of trial arm, and multivariable logistic regression analyses to investigate associations between patient characteristics and chosen trial arm. RESULTS: Of 377 women included, 76% chose AS and 24% CT. Most frequently cited reasons for AS were "treatment is not (yet) necessary" (59%) and trust in the AS-plan (39%). Reasons for CT were cancer worry (51%) and perceived certainty (29%). Women opting for AS more often had lower educational levels (OR 0.45; 95% confidence interval [CI], 0.22-0.93) and more often reported experiencing shared decision making (OR 2.71; 95% CI, 1.37-5.37) than women choosing CT. CONCLUSION: The LORD-trial is the first to offer women with low-risk DCIS a choice between CT and AS. Most women opted for AS and reported high levels of trust in the safety of AS. Their preferences highlight the necessity to establish the safety of AS for low-risk DCIS.

Factors associated with ductal carcinoma in situ (DCIS) treatment patterns and patient-reported outcomes across a large integrated health network.

PURPOSE: To examine associations between ductal carcinoma in situ (DCIS) patients' characteristics, treating locations and DCIS treatments received and to pilot assessing quality-of-life (QoL) values among DCIS patients with diverse backgrounds. METHODS: We performed a retrospective tumor registry review of all patients diagnosed and treated with DCIS from 2018 to 2019 in the UPMC-integrated network throughout central and western Pennsylvania. Demographics, clinical information, and administered treatments were compiled from tumor registry records. We categorized contextual factors such as different hospital setting (academic vs. community), socioeconomic status based on the neighborhood deprivation index (NDI) as well as age and race. QoL survey was administered to DCIS patients with diverse backgrounds via QoL questionnaire breast cancer module 23 and qualitative assessment questions. RESULTS: A total of 912 patients were reviewed. There were no treatment differences noted for age, race, or NDI. Mastectomy rate was higher in academic sites than community sites (29 vs. 20.4%; p = 0.0045), while hormone therapy (HT) utilization rate was higher in community sites (74 vs. 62%; p = 0.0012). QoL survey response rate was 32%. Only HT side effects negatively affected in QoL scores and there was no significant difference in QoL domains and decision-making process between races, age, NDI, treatment groups, and treatment locations. CONCLUSION: Our integrated health network did not show chronically noted disparities arising from social determinates of health for DCIS treatments by implementing clinical pathways and system-wide peer review. Also, we demonstrated feasibility in collecting QoL for DCIS women with diverse backgrounds and different socioeconomic statuses.

Patient Preferences for Outcomes Following DCIS Management Strategies: A Discrete Choice Experiment.

PURPOSE: Ductal carcinoma in situ (DCIS), a nonobligate precursor of breast cancer, is often aggressively managed with multimodal therapy. However, there is limited research on patients' preferences for trade-offs among treatment-related outcomes such as breast appearance, side effects, and future cancer risk. We sought to investigate whether women consider treatment features aside from cancer risk when making treatment choices for ductal carcinoma in situ and if so, to what degree other features influence these decisions. METHODS: A discrete choice experiment was administered to participants in a comprehensive cancer screening mammography clinic. The experimental design was used to generate constructed health profiles resulting from different management strategies. Health profiles were defined by breast appearance, severity of infection within the first year, chronic pain, hot flashes, and risk of developing or dying from breast cancer within 10 years. RESULTS: One hundred ninety-four women without a personal history of breast cancer completed the choice task. Across 10 choice questions, 29% always selected the health profile with a lower risk of invasive breast cancer (ie, dominated on cancer risk), regardless of the effects of treatment. For nonrisk dominators, breast cancer risk remained the most important factor but was closely followed by chronic pain (24% [95% CI, 20 to 28]) and infection (22% [95% CI, 18 to 25]). Depending on treatment outcomes, the tolerable increase in breast cancer risk was as high as 3.4%. CONCLUSION: Most women were willing to make some trade-offs between invasive cancer risk and treatment-related outcomes. Our findings highlight the importance of shared decision-making weighing risks and benefits between patient and provider management of low-risk disease.

The effect of treatment on patient-reported distress after breast cancer diagnosis.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) uses a 10-point scale (in which 0 indicates no distress and 10 indicates extreme distress) to measure patient-reported distress. In the current study, the authors sought to examine the relationship between treatment and NCCN DT scores in patients with breast cancer over time. METHODS: The authors included women aged ≥18 years who were diagnosed with stage 0 to stage IV breast cancer (according to the seventh edition of the American Joint Commission on Cancer staging system) at a 3-hospital health system from January 2014 to July 2016. Linear mixed effects models adjusted for covariates including stage of disease, race/ethnicity, insurance, and treatment sequence (neoadjuvant vs adjuvant) were used to estimate adjusted mean changes in the DT score (MSCs) per week for patients undergoing lumpectomy, mastectomy only, and mastectomy with reconstruction (MR). RESULTS: The authors analyzed 12,569 encounters for 1029 unique patients (median score, 4; median follow-up, 67 weeks). Patients treated with MR (118 patients) were younger and more likely to be married, white, and privately insured compared with patients undergoing lumpectomy (620 patients) and mastectomy only (291 patients) (all P < .01). After adjusting for covariates, distress scores were found to decline significantly across all 3 surgical cohorts, with patients undergoing MR found to have both the most preoperative distress and the greatest decline in distress prior to surgery (MSC/week: -0.073 for MR vs -0.031 for lumpectomy vs -0.033 for mastectomy only; P = .001). Neoadjuvant therapy was associated with a longitudinal decline in distress for patients treated with lumpectomy (-1.023) and mastectomy only (-0.964). Over time, ductal carcinoma in situ (-0.503) and black race (-1.198) were found to be associated with declining distress among patients treated with lumpectomy and MR, respectively, whereas divorced patients who were treated with mastectomy only (0.948) and single patients treated with lumpectomy (0.476) experienced increased distress (all P < .05). CONCLUSIONS: When examined longitudinally in consecutive patients, the NCCN DT can provide patient-reported data to inform expectations and guide targeted support for patients with breast cancer.

Secondary breast carcinoma after completely remitted chronic myeloid leukemia following targeted tyrosine kinase inhibitor therapy.

We describe a rare case of secondary breast carcinoma after chronic myeloid leukemia (CML) in a 56-year-old woman. The patient was treated with hydroxyurea and imatinib for CML and achieved complete remission (she has since been taking imatinib as the maintenance therapy). Four years later, the patient noticed a firm and painless lump in the left breast, which was diagnosed as ductal carcinoma in situ based on a percutaneous biopsy of the mass. Simple resection and sentinel lymph node biopsy of the left breast were then performed. Pathological studies revealed a medium-grade intraductal carcinoma, with local infiltration associated with invasive micropapillary carcinoma. She received adjuvant endocrine therapy with imatinib after surgery. Breast cancer secondary to CML (treated with imatinib and completely remitted) is extremely rare. This report provides evidence to assist in the diagnosis and treatment for this rare manifestation.

Sentinel lymph node biopsy and aberrant lymphatic drainage in recurrent breast cancer: Findings likely to change treatment decisions.

BACKGROUND AND OBJECTIVES: It is not clear whether sentinel lymph node biopsy (SLNB) can be applied to patients with a second breast cancer or recurrence occurring at previously treated breast. The purpose of this study was to assess the feasibility of SLNB procedure in patients with recurrent breast cancer. METHODS: Patients with non-metastatic recurrent N0 breast cancer at ipsilateral breast were included. Patients were grouped according to their initial breast, axilla, and overall surgery. Presence of drainage and its pattern as well as SLNB success rate and overall axillary involvement rates were assessed. Findings were compared. RESULTS: Out of 75 patients, mean age was 52.5 years and disease-free interval was 82 (9-312) months. Lymphatic drainage was successful in 42 (56%) patients. Drainage positivity was more frequent in patients who were previously treated with SLNB (82.6%) than in patients who underwent axillary lymph node dissection (ALND) (44.2%; P = 0,002). Aberrant lymphatic drainage was detected in 64.3% of drainage positive patients. Success rate of reoperative SLNB was 92.9%. Adjuvant treatment plan was altered in 12 (16%) patients. In 15 patients, negative SLNB prevented axillary dissection. CONCLUSIONS: Reoperative SLNB seems to be technically feasible in N0 recurrent breast cancer patients. It may further avoid unnecessary ALND and lead changes in adjuvant treatment plans. J. Surg. Oncol. 2016;114:796-802. © 2016 2016 Wiley Periodicals, Inc.

Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015.

The 14th St Gallen International Breast Cancer Conference (2015) reviewed substantial new evidence on locoregional and systemic therapies for early breast cancer. Further experience has supported the adequacy of tumor margins defined as 'no ink on invasive tumor or DCIS' and the safety of omitting axillary dissection in specific cohorts. Radiotherapy trials support irradiation of regional nodes in node-positive disease. Considering subdivisions within luminal disease, the Panel was more concerned with indications for the use of specific therapies, rather than surrogate identification of intrinsic subtypes as measured by multiparameter molecular tests. For the treatment of HER2-positive disease in patients with node-negative cancers up to 1 cm, the Panel endorsed a simplified regimen comprising paclitaxel and trastuzumab without anthracycline as adjuvant therapy. For premenopausal patients with endocrine responsive disease, the Panel endorsed the role of ovarian function suppression with either tamoxifen or exemestane for patients at higher risk. The Panel noted the value of an LHRH agonist given during chemotherapy for premenopausal women with ER-negative disease in protecting against premature ovarian failure and preserving fertility. The Panel noted increasing evidence for the prognostic value of commonly used multiparameter molecular markers, some of which also carried prognostic information for late relapse. The Panel noted that the results of such tests, where available, were frequently used to assist decisions about the inclusion of cytotoxic chemotherapy in the treatment of patients with luminal disease, but noted that threshold values had not been established for this purpose for any of these tests. Multiparameter molecular assays are expensive and therefore unavailable in much of the world. The majority of new breast cancer cases and breast cancer deaths now occur in less developed regions of the world. In these areas, less expensive pathology tests may provide valuable information. The Panel recommendations on treatment are not intended to apply to all patients, but rather to establish norms appropriate for the majority. Again, economic considerations may require that less expensive and only marginally less effective therapies may be necessary in less resourced areas. Panel recommendations do not imply unanimous agreement among Panel members. Indeed, very few of the 200 questions received 100% agreement from the Panel. In the text below, wording is intended to convey the strength of Panel support for each recommendation, while details of Panel voting on each question are available in supplementary Appendix S2, available at Annals of Oncology online.

Simultaneous breast and axillary recurrence in a patient with a history of breast cancer and ipsilateral upper extremity melanoma: challenges in diagnosis and management.

BACKGROUND: Nodal patterns of spread for breast cancer and melanoma have been extensively studied in the literature. The phenomenon of upper extremity melanoma and ipsilateral breast cancer has been previously reported. We describe a rare case of a simultaneous locoregional recurrence of both malignancies. CASE REPORT: A patient with a previous diagnosis of stage 1A melanoma of the left upper extremity at age 29 developed left breast invasive ductal carcinoma 1 year later. The patient underwent a wide local excision with negative margins for the melanoma and a partial mastectomy with axillary dissection followed by chemotherapy and radiation therapy for her breast cancer. Five years later she was diagnosed with a dual recurrence while 36 weeks pregnant. CONCLUSIONS: Regular follow-up according to the NCCN guidelines is critical in diagnosing a recurrence of malignancy. Pathologic analysis is paramount in dictating management strategies in rare cases of dual recurrence.

Relief from cancer chemotherapy side effects with pharmacologic vitamin C.

Fatigue is a common, often debilitating, side effect of cancer chemotherapy. Pharmacologic vitamin C has been used as an alternative treatment for the disease itself but its effects on fatigue have not often been documented. Here we report on the case of a woman with recurrent breast cancer, undergoing weekly chemotherapy, with lethargy as a major symptom. Vitamin C (50 g/session) was administered twice weekly and quality of life and multidimensional fatigue symptomology questionnaires were undertaken. Dramatic decreases in fatigue and insomnia were observed, as well as increased cognitive functioning. There were no adverse side effects of i.v. vitamin C.

Regression of ductal carcinoma in situ after treatment with acupuncture.

This report describes a case of ductal carcinoma in situ (DCIS) that regressed after treatment with acupuncture, Chinese herbs, and other complementary and alternative medicine (CAM). The natural history of DCIS remains to be elucidated, and it is unclear whether all DCIS cases progress to invasive breast cancer. Surgery plus radiation therapy or mastectomy is recommended for women in whom this potentially nonprogressive cancer is detected. This case supports the developing trend toward active surveillance in lieu of breast-disfiguring surgery and offers evidence that CAM therapies may be of value in preventing progression of DCIS to invasive breast cancer.

Fatigue, inflammation, and ω-3 and ω-6 fatty acid intake among breast cancer survivors.

PURPOSE: Evidence suggests that inflammation may drive fatigue in cancer survivors. Research in healthy populations has shown reduced inflammation with higher dietary intake of ω-3 polyunsaturated fatty acids (PUFAs), which could potentially reduce fatigue. This study investigated fatigue, inflammation, and intake of ω-3 and ω-6 PUFAs among breast cancer survivors. METHODS: Six hundred thirty-three survivors (mean age, 56 years; stage I to IIIA) participating in the Health, Eating, Activity, and Lifestyle Study completed a food frequency/dietary supplement questionnaire and provided a blood sample assayed for C-reactive protein (CRP) and serum amyloid A (30 months after diagnosis) and completed the Piper Fatigue Scale and Short Form-36 (SF-36) vitality scale (39 months after diagnosis). Analysis of covariance and logistic regression models tested relationships between inflammation and fatigue, inflammation and ω-3 and ω-6 PUFA intake, and PUFA intake and fatigue, controlling for three incremental levels of confounders. Fatigue was analyzed continuously (Piper scales) and dichotomously (SF-36 vitality ≤ 50). RESULTS: Behavioral (P = .003) and sensory (P = .001) fatigue scale scores were higher by increasing CRP tertile; relationships were attenuated after adjustment for medication use and comorbidity. Survivors with high CRP had 1.8 times greater odds of fatigue after full adjustment (P < .05). Higher intake of ω-6 relative to ω-3 PUFAs was associated with greater CRP (P = .01 after full adjustment) and greater odds of fatigue (odds ratio, 2.6 for the highest v lowest intake; P < .05). CONCLUSION: Results link higher intake of ω-3 PUFAs, decreased inflammation, and decreased physical aspects of fatigue. Future studies should test whether ω-3 supplementation may reduce fatigue among significantly fatigued breast cancer survivors.

Selecting high priority quality measures for breast cancer quality improvement.

BACKGROUND: Although many quality measures have been created, there is no consensus regarding which are the most important. We sought to develop a simple, explicit strategy for prioritizing breast cancer quality measures based on their potential to highlight areas where quality improvement efforts could most impact a population. METHODS: Using performance data for 9019 breast cancer patients treated at 10 National Comprehensive Cancer Network institutions, we assessed concordance relative to 30 reliable, valid breast cancer process-based treatment measures. We identified 4 attributes that indicated there was room for improvement and characterized the extent of burden imposed by failing to follow each measure: number of nonconcordant patients, concordance across all institutions, highest concordance at any 1 institution, and magnitude of benefit associated with concordant care. For each measure, we used data from the concordance analyses to derive the first 3 attributes and surveyed expert breast cancer physicians to estimate the fourth. A simple algorithm incorporated these attributes and produced a final score for each measure; these scores were used to rank the measures. RESULTS: We successfully prioritized quality measures using explicit, objective methods and actual performance data. The number of nonconcordant patients had the greatest influence on the rankings. The highest-ranking measures recommended chemotherapy and hormone therapy for hormone-receptor positive tumors and radiation therapy after breast-conserving surgery. CONCLUSIONS: This simple, explicit approach is a significant departure from methods used previously, and effectively identifies breast cancer quality measures that have broad clinical relevance. Systematically prioritizing quality measures could increase the efficiency and efficacy of quality improvement efforts and substantially improve outcomes.

Fatal chemotherapy-induced encephalopathy following high-dose therapy for metastatic breast cancer: a case report and review of the literature.

Chemotherapy-induced encephalopathies occur in a variety of clinical settings and the most detailed accounts have been described following combination methotrexate and radiation therapy. The case described herein developed severe encephalopathy following a high-dose chemotherapy protocol used in the treatment of metastatic carcinoma of the breast. Visual symptoms developed 3 weeks after completing high-dose chemotherapy and peripheral blood hematopoietic stem cell transplantation. Over the next several weeks, additional neurologic deficits developed and continued to progress despite various treatment interventions. Diffuse deep gray matter damage was identified on MR imaging and a brain biopsy revealed pathological findings similar in many respects to those described for methotrexate/radiation, cisplatin, BCNU and/or 5 FU/levamisole-related leukoencephalopathy. The patient succumbed to complications resulting from the CNS disorder, 8 weeks after the onset of symptoms. This case is unusual for two reasons. First, the patient developed severe encephalopathy following a high-dose chemotherapy protocol commonly used in the treatment of metastatic breast carcinoma and second, the encephalopathy involved primarily deep gray matter structures rather than white matter.

"Well, have I got cancer or haven't I?" The psycho-social issues for women diagnosed with ductal carcinoma in situ.

OBJECTIVES: To explore women's experience of being diagnosed with ductal carcinoma in situ (DCIS) in relation to the following: response to the diagnosis; understanding about the diagnosis; satisfaction with information; satisfaction with the level of involvement in treatment decision-making and satisfaction with support services. DESIGN: An explorative descriptive qualitative design was used to facilitate an in-depth exploration of women's experiences. SETTING AND PARTICIPANTS: Five focus group interviews were conducted in New South Wales (NSW), Australia, involving 26 women diagnosed with DCIS. RESULTS: DCIS is a non-invasive breast disease, that in most cases will not recur if treated, and cannot of itself metastasize to other parts of the body. However, this study found that women were confused about whether or not they had cancer that could result in death. Women's confusion was compounded by the use of the term "carcinoma" and by the recommendation of treatments such as mastectomy. Women's confusion was not alleviated by appropriate information, with most women reporting dissatisfaction with the information they received specifically about DCIS. CONCLUSIONS: This study identifies that a diagnosis of DCIS has a significant psychological impact on women. The communication challenges highlighted in this study are not only relevant to DCIS but to any other disease in which the natural history is uncertain and the evidence about treatment effectiveness is still emerging. Further research is needed in areas such as DCIS to explore the difficulties experienced in doctor-patient communication and their impact on patient outcomes, and how to optimize doctor-patient communication.