Management Of Dcis After Primary Treatment
DCIS falls between atypical ductal hyperplasia and invasive ductal carcinoma within the spectrum of breast proliferative abnormalities. The Breast Cancer Prevention Trial performed by NSABP showed a 75% reduction in the occurrence of invasive breast cancer in patients with ADH treated with tamoxifen.54,55 These data also showed that tamoxifen led to a substantial reduction in the risk of developing invasive breast disease.56 The Early Breast Cancer Trialists Collaborative Group overview analysis showed that, with 5 years of tamoxifen therapy, patients with ER-positive or receptor-unknown invasive tumors had a 39% reduction in the annual odds of recurrence of invasive breast cancer.57
A phase III trial randomized patients with excised DCIS to receive WBRT or no WBRT and tamoxifen versus no tamoxifen.20 The randomization was independent for each of the 2 treatments . With 12.7 years of median follow-up, the use of tamoxifen decreased all new breast events . The use of tamoxifen decreased ipsilateral and contralateral breast events in the subjects not given WBRT , but not in those receiving WBRT .
Results of the IBIS-II and the NSABP-B-35 studies indicate that anastrozole provides at least a comparable benefit as adjuvant treatment for postmenopausal patients with hormone-receptor-positive DCIS treated with BCS and RT, with a different toxicity profile.
NCCN Recommendations for Management of DCIS After Primary Treatment
Nccn Patient Resources For Breast Cancer
NCCN patient resources are based on the same treatment information your doctors use and help you talk to your doctor about the best treatment options for your disease.
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Brca Testing And Variant Status
Among the 410 patients included in this study, 384 were tested for BRCA1/BRCA2 variants 24 were not tested, and 2 had an unknown testing status . For 75% of the 24 patients who were not tested, physicians deemed that genetic testing would have had no impact on medical management . The testing rate was 100% among female patients with at least one close blood relative with a BRCA pathogenic variant , female patients with a diagnosis of breast cancer before age 50 who had an additional primary breast cancer , and female patients with a personal history of ovarian cancer . Testing rates over the study period were assessed by year, and tended to range from 88 to 95% from 2013 to 2017, suggesting there was no major change in testing rates over the study period .
Table 3 Testing for BRCA Pathogenic Variants in Accordance with NCCN Guidelinesa in All Patients
Female patients with male-relative related risk factors had slightly lower testing rates. For example, female patients diagnosed at age50years with at least one close blood relative with prostate cancer , had a lower testing rate of 87% and female patients with at least one close male blood relative with breast cancer had the lowest testing rate of 78% . Testing rates were also stratified by year to assess trends over the course of the study period. Due to the small sample size for each of the high risk groups in each year, no clear trends were discernable .
Recommended Reading: Nccn Guidelines For Breast Cancer
Regional Nodal Irradiation After Bcs
The reduction in the risk of locoregional and distant recurrence and improvement in DFS seen in the MA.20 and EORTC 22922/10925 trials,181,182 and the reduction in breast cancer mortality with 15-year follow-up of the EORTC 22922 patients,183 support the importance of RNI after BCS.
Clinical judgment is needed when determining inclusion of the internal mammary nodes during RNI. Therefore, the NCCN Panel no longer specifies the fields that should be included for RNI and refers to it as comprehensive RNI. According to the panel, patient selection should consider risks versus benefits, including long-term organ toxicities, comorbidities of the patient, age, and life expectancy. In including RT to the internal mammary nodes, meticulous treatment planning with normal tissue dose constraints is mandatory.
RNI After BCS for Node-Negative Disease
The NCCN Panel recommends consideration of comprehensive RNI in patients with central/medial tumors and in accordance with the MA.20 criteria-T3 tumors, as well as those with T2 tumors who have undergone limited axillary dissection and also have other risk factors, including high-grade histology, ER-negative disease, or extensive lymphovascular invasion.181
RNI After BCS for Node-Positive Disease
For those with 4 positive nodes, the NCCN Panel recommends comprehensive RNI with inclusion of any portion of the undissected axilla at risk .
RT After BCS in Older Adults With ER-Positive Tumors
Adjuvant RT After Mastectomy
Workup For Nonmetastatic Invasive Breast Cancer
The recommended workup of localized invasive breast cancer includes a history and physical exam. Complete blood count and liver function tests have no added benefit in the detection of underlying metastatic disease in asymptomatic patients with early-stage breast cancer.62 In addition, monitoring of disease relapse with any tumor markers is not recommended.
Imaging with bilateral diagnostic mammography is recommended breast ultrasonography is recommended only if necessary.
The use of MRI in the workup remains controversial. Breast MRI advocates note its high sensitivity for evaluation of extent of disease, particularly for invasive cancer and in dense breasts where mammographically occult disease is more likely to elude preoperative detection. MRI detractors note that MRI has a high percentage of false-positive findings, resulting in further diagnostic workup including MRI-guided biopsyin many circumstances.6365 MRI findings tend to overestimate extent of disease,66 resulting in increased frequency of mastectomies.6770
MRI findings alone are not sufficient to determine whether BCT is optimal as additional tissue sampling is needed to verify true malignant disease warranting excision. MRI use may increase mastectomy rates by identifying areas of mammographically occult disease that may have been adequately treated with radiation after BCS had the disease remained undiscovered without MRI.70
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Systemic Therapy For Recurrent Or Stage Iv Hr
Women with stage IV or recurrent disease characterized by HR-positive, HER2-positive tumors have the option of receiving HER2-directed therapy as a component of their treatment plan. Options include treatment with a HER2-targeted therapy plus chemotherapy or endocrine therapy alone or in combination with HER2-targeted therapy. Endocrine therapy alone or in combination with HER2-targeted therapy is a less toxic approach compared with HER2-targeted therapy combined with chemotherapy. Premenopausal women treated with HER2-targeted therapy and endocrine therapy should receive ovarian suppression or ablation.
Adding trastuzumab or lapatinib to an AI has demonstrated a PFS advantage compared with AI alone in postmenopausal women with stage IV or recurrent HR-positive, HER2-positive tumors.
In the TAnDEM study, postmenopausal women with metastatic HR-positive and HER2-positive tumors were randomized to receive anastrozole alone or anastrozole plus trastuzumab.105 Compared with single-agent anastrozole, an improvement in PFS was seen with combination therapy . The combination was associated with a higher incidence of toxicities , fatigue , diarrhea , vomiting , and pyrexia serious toxicities were rare in both treatment arms.
Systemic Therapy For Stage Iv Or Recurrent Hr
For patients with HER2-positive, HR-negative recurrent/stage IV breast cancer, the treatment approach is HER2-targeted therapy in combination with systemic chemotherapy. The NCCN panel notes that an FDA-approved biosimilar is an appropriate substitute for trastuzumab. Also, trastuzumab and hyaluronidase-oysk injection for subcutaneous use may be substituted for trastuzumab. This subcutaneous option has different dosage and administration instructions compared with intravenous trastuzumab. Doses and schedules of representative regimens for use in HER2-positive metastatic breast cancer are also included in NCCN Guidelines.
Patients progressing on a HER2-targeted therapy should be offered additional subsequent treatment with a HER2-targeted therapy since it is beneficial to continue suppression of the HER2 pathway. The choice of the HER2-targeted therapy will depend on previously administered therapy, relapse-free interval, and patients preference and access.
The optimal sequence of available HER2-targeted therapies and the optimal duration of HER2-targeted therapy for recurrent/stage IV is currently unknown. The NCCN panel recommends continuing HER2-targted therapy until progression or unacceptable toxicity.
Preferred Regimens for Stage IV/Recurrent HER2-Positive Breast Cancer
Other Regimens for Stage IV/Recurrent HER2-Positive Breast Cancer
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Additional Targeted Therapies For Stage Iv Disease Useful In Certain Circumstances
Neurotrophic tropomyosin receptor kinase gene fusions are seen in a few rare types of cancer, such as secretory carcinoma of the breast or salivary gland and infantile fibrosarcoma and also infrequently in some common cancers, such as melanoma, glioma, and carcinomas of the thyroid, lung, and colon.172NTRK fusions are identified by fluorescence in situ hybridization, next generation sequencing, or polymerase chain reaction. Larotrectinib173175 and entrectinib175,176 are 2 NTRK-inhibitors that are FDA approved for the treatment of solid tumors that have an NTRK gene fusion without a known acquired resistance mutation and have no satisfactory alternative treatments or that have progressed following treatment. If a patient with recurrent or stage IV breast cancer presents with a tumor with an NTRK fusion, treatment with an NTRK inhibitor is an option if no satisfactory alternative treatment exists or that have progressed following treatment.
Systemic Therapy For Stage Iv Or Recurrent Metastatic Hr
Women with stage IV or recurrent disease characterized by HR-positive, HER2-negative tumors with no visceral crisis are treated with endocrine therapy alone or endocrine therapy in combination with targeted agents.
Women whose disease progresses after a year from the end of adjuvant endocrine-based therapy and those who present with de novo stage IV/metastatic breast cancer are eligible for first-line endocrine therapies.
Many premenopausal and postmenopausal women with HR-positive breast cancer benefit from sequential use of endocrine therapies at disease progression. Therefore, women with breast cancers who respond to an endocrine-based therapy with either shrinkage of the tumor or long-term disease stabilization should receive additional endocrine therapy at disease progression. Those who progress on or within 12 months of completing adjuvant endocrine therapy or patients who progress on first-line endocrine therapy for metastatic disease are eligible for second-line endocrine therapy either as monotherapy or in combination with a targeted agent. The optimal sequence for endocrine therapy is not well defined. The choice would depend on previous therapy, tolerance of treatment, and patient preference.
Preferred First-Line Therapy for HR-Positive, HER2-Negative Breast Cancer
Aromatase Inhibitor in Combination With Cyclin-Dependent Kinase 4/6 Inhibitor
Single Agent Fulvestrant
Fulvestrant + CDK 4/6 Inhibitor
Fulvestrant + Nonsteroidal AI
Monotherapy With Endocrine Agents
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New Nccn Guidelines For Mammography: All Women Over 40
Sharon Worcester, MA
New evidence-based patient-facing breast cancer guidelines from the National Comprehensive Cancer Network call for annual mammograms for all average-risk women over age 40 years.
This simplifies the message, says the NCCN.
“There are many, often conflicting, recommendations surrounding breast cancer screening, which causes a lot of confusion and apprehension,” commented Therese Bevers, MD, professor of clinical cancer prevention at the University of Texas MD Anderson Cancer Center and chair of the guidelines panel
“These are the latest, evidence-based guidelines from experts in the field of breast cancer screening and diagnosis from more than two dozen leading cancer centers in the United States,” she said in a statement.
The NCCN guidelines, Breast Cancer Screening and Diagnosis, were published “to help people understand their personal risk for breast cancer, when they should begin screening, and how often to screen in order to detect cancer earlier, for more treatment options and better outcomes,” the organization explained in its press release.
An earlier start may be recommended for those with additional risk factors, Bevers noted. Screening is also important for those who are pregnant or breastfeeding.
Nccn Now Recommends Breast Cancer Index For Predicting Benefit From Extended Endocrine Therapy
The Breast Cancer Index assay is the only of its kind to be recommended in the National Comprehensive Cancer Network Guidelines for the treatment of breast cancer as being predictive of extended adjuvant endocrine therapy.
Breast Cancer Index , a molecular gene expressionbased test used for determining which patients with early-stage, hormone receptor positive breast cancer benefit from extended endocrine therapy, is now included in the National Comprehensive Cancer Network Guidelines for breast cancer, according to Biotheranostics, Inc.1
Per NCCN recommendations, BCI can be used for consideration of extended adjuvant endocrine therapy with a 2A category of evidence and consensus, which indicates uniform consensus from the organization that the recommendation is appropriate.
Clinical guideline endorsement by the NCCN Panel marks an evidentiary milestone for the Breast Cancer Index underscoring its distinct clinical utility for women with HR early-stage breast cancer, and a new paradigm for the use of genomic assays to aid in endocrine decision-making, Catherine Schnabel, PhD, chief scientific officer of Biotheranostics, stated in a press release.With NCCN Guidelines as the recognized benchmark for cancer policy, the positive recommendation of BCI as a predictive biomarker of extended endocrine benefit will allow increased patient access to this important genomic tool.
Evaluating The Performance Of National Comprehensive Cancer Network Breast And Ovarian Genetic/familial High Risk Assessment Referral Criteria For Breast Cancer Women In An Asian Surgical Breast Clinic
Geok-Hoon Lim1,2, Eillen Borje1, John C. Allen Jr3
1Breast Department, KK Womens and Childrens Hospital, Singapore 229899, Singapore 2Duke-NUS Graduate Medical School, Singapore 169857, Singapore 3Centre for Quantitative Medicine, Duke NUS Graduate Medical School, Singapore 169857, Singapore
Contributions: Conception and design: GH Lim Administrative support: All authors Provision of study materials or patients: GH Lim, E Borje Collection and assembly of data: E Borje Data analysis and interpretation: All authors Manuscript writing: All authors Final approval of manuscript: All authors.
Background: Globally, resources for genomic services vary. Current National Comprehensive Cancer Network breast and ovarian genetic/familial high risk assessment criteria for further genetic risk evaluation are useful, but lack specificity for reliably excluding patients with low a priori risk. This may result in patient overload in lesser-equipped genetics clinics. Since we use Manchester and the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm risk assessment models in our genetics clinic to determine whether genetic testing is warranted, we chose Manchester and BOADICEA as the reference standard to compare how the NCCN breast and ovarian genetic/familial high risk assessment criteria for further genetic risk evaluation performs against these two risk assessment models in referring breast cancer patients for genetic evaluation.
Data Source Study Design And Population
An online physician panel approach was used to recruit medical oncologists for this retrospective chart review study, conducted from June 2017 to April 2018. Cardinal Health Specialty Solutions sent open invitations to its panel of community-based oncologists who treat breast cancer in the US. Eligible oncologists were required to be able to participate in research approved by a central institutional review board and to have treated at least one patient with breast cancer in the past year.
The primary outcomes of the study were BRCA testing status and results of testing. In addition, data on physician characteristics and patient characteristics were also collected through the eCRF.
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Preferred Regimens For Second And Subsequent Lines Of Therapy For Hr
Fulvestrant + CDK 4/6 Inhibitors
Fulvestrant in combination with a CDK 4/6 inhibitor may be offered to patients who experienced progression during prior treatment with AIs with or without 1 line of prior chemotherapy , because PFS was improved compared with fulvestrant alone in a phase III trial .54 The NCCN panel notes that treatment should be limited to those without prior exposure to CDK 4/6 inhibitors.
The phase III trial compared the combination of palbociclib and fulvestrant to fulvestrant in pre- or postmenopausal patients with HR-positive, HER2-negative advanced breast cancer whose disease progressed on prior endocrine therapy. Pre- or peri-menopausal patients also received goserelin. The median PFS was 9.5 months for the combination compared with 4.6 months for fulvestrant 55 Grade 3/4 adverse events of palbociclib and fulvestrant were mainly confined to neutropenia .
In the MONARCH 2 phase III trial, patients who had progressed while receiving endocrine therapy were randomly assigned to fulvestrant with or without abemaciclib.56 Those receiving combination therapy experienced an improved PFS relative to those receiving fulvestrant alone . The ORR was higher in those receiving abemaciclib and fulvestrant .56 In addition, an improvement was seen in OS with abemaciclib plus fulvestrant compared with fulvestrant alone .57
Fulvestrant Plus Alpelisib
Everolimus Plus Endocrine Therapy
Risk Of Mns Stratified By Treatment Modality
The combined analyses of all myeloid and lymphoid neoplasms are reported because the individual hazards for MN risk were comparable. A multivariable analysis compared the risk of developing an MN among three mutually exclusive treatment groups with the risk of breast cancer survivors treated with surgery alone, adjusting for NCCN site, age at breast cancer diagnosis, stage, and race. A nonsignificant increase in MN risk was observed in those treated with surgery plus radiation compared with surgery alone . However, there was a significant risk among patients treated with both surgery and chemotherapy and those treated with all three modalities . Consistent with prior reports,12,13 MN risk was not increased for patients also treated with a taxane versus patients not treated with a taxane .
Hazard ratios for risk of marrow neoplasm and incidence rates of marrow neoplasm per 1,000 person-years.
After 109,560 person-years of follow-up, the overall rate of MN was 0.46 per 1,000 person-years . Similar rates were observed in the subsets treated with surgery and radiation , surgery and chemotherapy , or all three modalities , in contrast with surgery alone . There was a continuous increase in the cumulative incidence of MN, with half of the 50 MNs occurring between years 6 and 10. The cumulative frequency after 10 years was twice the cumulative frequency observed after 5 years .
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