Kembara Xtra - Medicine - Ductal Carcinoma In Situ Introduction Ductal carcinoma in situ (DCIS) is a diverse group of lesions that are limited to ducts and lobules and are characterized by a clonal proliferation of neoplastic, noninvasive epithelial cells. It is thought of as a premalignant lesion and can be low, moderate, or high grade. It is uncommon for DCIS to proceed to invasive breast cancer (IBC), regardless of the histologic type or kind of treatment. Epidemiology (Incidence and Prevalence) Incident: 1% annualized rise in the average Estimated 62,738 new diagnoses of DCIS in 2019; projected 49,290 new diagnoses in 2021; and estimated 62,738 new diagnoses of DCIS in 2019. DCIS makes up about 80–85% of in situ breast carcinomas, while lobular carcinoma in situ (LCIS) makes up about 15%. Represents around 26% of all new cases of breast cancer; incidence rates are comparable across ethnic groups; incidence is more stable in women between the ages of 50 and 69; and incidence is rising in women between the ages of 50 and 70. Pathophysiology and Etiology A non-obligatory predecessor to IBC; poorly understood spectrum of polyclonal and clonal epithelial proliferative lesions; last stage before IBC; poorly understood alterations required for the transition to IBC. According to molecular research, high- and low-grade DCIS are genetically different lesions. - High-grade DCIS is linked to a greater risk of developing into an invasive condition. Genetics Estrogen receptor (ER) and progesterone receptor (PR) are frequently expressed in low-grade DCIS, while HER2 protein overexpression or amplification is not. High-grade DCIS is not always ER+ or PR+. - HER2 protein overexpression and amplification are widespread (even more so than IBC), and they are frequently linked to p53 gene alterations. BRCA1 and BRCA2 correlations have been found; high-risk DCIS patients should think about genetic counseling. Risk Elements Female gender, nulliparity, late age at first birth or menopause, first-degree relatives with breast cancer, long-term use of postmenopausal combined estrogen and progestin therapy, history of atypical ductal hyperplasia (ADH), and dense breast tissue are all risk factors, though they are not as strongly associated as those for IBC. The relationship between oral contraceptive use and age, body mass index, smoking, lactation, early menarche, and alcohol use is less certain. Prevention With little to no decrease in the frequency of advanced malignancies, screening may lead to overdiagnosis. A risk assessment tool is provided at http://bcrisktool.cancer.gov for women who are at higher risk. The USPSTF's general screening recommendations are as follows: - Biannual mammograms for females 50 to 74 years old (B recommended) - Every woman's decision to begin mammography screening at age 50 should be her own. - There is insufficient data to determine if screening mammography is beneficial or harmful for women under 75. - Inadequate data to evaluate the advantages and disadvantages of digital breast tomosynthesis (DBT) as a primary screening technique (I statement). - There is insufficient data to determine the relative merits and drawbacks of supplementary screening in women with dense breasts who have otherwise negative screening mammograms using breast ultrasonography (US), magnetic resonance imaging (MRI), DBT, or other techniques. The National Comprehensive Cancer Network (NCCN) has general screening recommendations: - Women should be aware of their breasts and report changes right away. Periodic, regular breast self-examination (BSE) may help with this. Clinical breast examination (CBE) According to USPSTF, there is not enough data to determine the advantages and disadvantages of a mammography screening supplement for women under the age of 40. According to the WHO, CBE may be helpful for women between the ages of 50 and 69 in areas with poor health infrastructure (mammography not readily available). Risk reduction: - Evaluate familial/genetic history. - Perform BSE with CBE every 1 to 3 years from ages 25 to 39. - Perform annual CBE in women starting at age 40. - Lifestyle changes: Exercise, maintain a nutritious diet, limit alcohol use to one drink per day, and manage your weight. - Tamoxifen is advised for premenopausal women and raloxifene for postmenopausal women who are high-risk and under 35 years old. - Aromatase inhibitors' advantages are less obvious. The majority of DCIS are now detected by screening mammography (microcalcifications are present in about 72% of cases), while 12% of patients may be asymptomatic and have nonpalpable masses. A palpable lump, spontaneous nipple discharge, or Paget disease may indicate more advanced lesions. clinical assessment CBE in both the supine and upright positions with the patient; checking for nipple retraction/excoriation (Paget disease), asymmetry, spontaneous discharge, and skin abnormalities (peau d'orange, erythema, scaling). Complete breast palpation, including cervical, supraclavicular, and axillary lymph node examination Promising clinical results: Unless 30 years old and with a low clinical suspicion, refer for consideration of diagnostic imaging and/or surgical examination (monitor 1–2 menstrual cycles; refer if clinical findings persist). Multiple Diagnoses ADH, LCIS, microinvasive cancer, flat epithelial atypia, common ductal hyperplasia, Results of the first imaging and laboratory tests, including mammography The American Radiology Society has produced a quality assurance (QA) technique called BI-RADS: Breast Imaging-Reporting and Data System. – Breast US and MRI interpretation are now included with BI-RADS. – Parts of the BI-RADS report: The purpose of the study and the sort of test Breast density is included in the overall breast composition, which includes the following: A—almost all of the breast tissue is fatty tissue; B—scattered patches of fibroglandular density; C—heterogeneously dense; D—extremely dense. Uses common BI-RADS descriptors to describe anomalies and significant results A summary report that includes the final BI-RADS assessment category and a comparison to earlier images – final suggestions for BI-RADS assessment category and screening: BI-RADS 0: incomplete; further imaging evaluation required; frequently seen on screening tests; take into account diagnostic workup. BI-RADS 1: unfavorable Continue using the screening recommendations in effect. BI-RADS 2: harmless No more action is required; keep using the screening procedures as is. BI-RADS 3: likely benign, 2% chance of cancer For the first year, follow-up imaging should be done every six months; for the following year, imaging should be done every six to twelve months. If the patient is worried or the follow-up is unknown, biopsy may be considered. The patient and doctor should talk about potential management strategies and probably a biopsy. Highly indicative of malignancy, BI-RADS 5 Need for diagnostic imaging, followed by a biopsy, and BI-RADS 6: known biopsy—proven cancer Include patients who have biopsy-confirmed malignancies that haven't been surgically removed; DCIS is most frequently seen as clustered microcalcifications; tissue biopsy should be considered after diagnostic imaging. Tests in the Future & Special Considerations US is not normally suggested for screening; breast MRI screening is more sensitive than mammography; this leads to a higher incidence of false positives; and screening MRI is only advised in select women: - BRCA mutation—starts between the ages of 25 and 29 - First-degree relatives of BRCA carriers—start between the ages of 25 and 29 - Models mostly based on family history define a lifetime risk of breast cancer of 20%.—annual breast MRIs starting 10 years before the youngest member of the family but not before age 25. Thoracic radiation should be administered between the ages of 10 and 30. Annual breast MRIs should start 10 years after radiation treatment, but not before age 25. - The patient or first-degree family has Li-Fraumeni, PTEN, or Bannayan-Riley-Ruvalcaba syndrome. - The following genes and/or risk levels are associated with a 20% chance of breast cancer: ATM, CDH1, CHEK2, PALB2, PTEN, STK11, TP53. Breast MRI was recommended by the NCCN Panel during the initial evaluation of DCIS. Pathology - Tissue is required for diagnosis and is commonly obtained by vacuum-assisted (VA) or core needle (CN) biopsy techniques that are guided by mammographic/stereotactic, US, or MRI images. Patients who are unsuitable for CN or VA biopsy may have open surgical biopsy, however this is uncommon. - Fine-needle aspiration (FNA) is insufficient for a precise DCIS diagnosis. - Histologic classification: Based on architectural patterns (comedo, solid, cribriform, clinging, papillary, and micropapillary), nuclear grade (I, II, or III), and the presence or absence of necrosis, tissues are categorized as low, middle, or high grade. A different histologic categorization that uses size as a defining characteristic is called ductal intraepithelial neoplasia (DIN). The grade has a greater impact on prognosis, progression risk, and local recurrence. High-grade DCIS frequently exhibits comedo-type necrosis (necrosis filling center portion of affected duct), while other forms of DCIS exhibit variable degrees of necrosis. - Establishing the ER and PR status Secondary chemoprevention after breast-conserving surgery for ER+ DCIS is used to manage the condition. - Tamoxifen for 5 years for postmenopausal individuals, or an aromatase inhibitor for premenopausal people. - Patients under 60 or those who are at risk for thromboembolism may benefit from aromatase inhibitor therapy. - Taken into account in lumpectomy patients who have received full breast radiotherapy or not. Chemotherapy after surgery is not recommended. Surgery is the main form of treatment, and the options for surgery depend on the likelihood of recurrence, the location of the organs involved, the severity of the disease, and the possibility of achieving "negative" margins. Positive margins are referred to as having "ink on tumor." The overwhelming body of evidence refutes the technique of obtaining negative margin widths greater than 2 mm. Margins less than 1 mm are deemed inadequate. If a patient chooses breast conservation, margins less than 1 mm at the breast fibroglandular boundary (chest wall or skin) may require a greater boost dosage of radiation. When determining the ideal margin width, DCIS with microinvasion, defined as no invasive focus larger than 1 mm in size, should be taken into account. Clinical judgment can be used to decide if reexcision may be avoided in specific cases when there is only minor or focal DCIS involvement close to the margin. The following surgical options are available: - Breast radiation therapy and lymph node dissection are not necessary for breast conservation (lumpectomy). - Breast conservation (lumpectomy), with or without boosting to the tumor bed, entire breast radiation therapy, and no lymph node operationIf the lumpectomy was performed in an area of the body that would make it difficult to execute a sentinel lymph node surgery in the future, a sentinel lymph node biopsy might be an option. - Total mastectomy should be performed on patients who are ineligible for margin-free lumpectomies. Mastectomy offers the most local control and can be performed with or without sentinel node biopsy and possible breast reconstruction. - In the absence of invasive cancer and established axillary metastatic disease, a thorough axillary lymph node dissection should not be carried out. - Long-term cause-specific survival appears to be equivalent to lumpectomy with whole breast radiotherapy. – In patients with ostensibly pure DCIS who are going to have a mastectomy, a sentinel lymph node biopsy should be taken into account. Radiation-related factors: - Radiation has a 50% reduction in recurrence rates but no overall survival advantage. – Radiation therapy has some drawbacks, such as the patient's burden of daily treatment for six weeks and transient side effects include weariness and skin toxicity. A somewhat elevated chance of acquiring secondary malignancies Impossibility of repeat radiation therapy in the ipsilateral breast in the event of invasive cancer. Considerations for DCIS recurrence: - Mastectomy is typically necessary for recurrence. – DCIS and IBC recurrence rates are comparable: Pure DCIS makes up 50% of recurrences, while IBC makes up 50%. – Wide local excision, chest wall radiation, and consideration of systemic hormone therapy should all be used to address recurrence. Following breast-conserving surgery for ER + DCIS, secondary chemoprevention: - Tamoxifen for 5 years for postmenopausal individuals, or an aromatase inhibitor for premenopausal people. - Patients under 60 years old or those who are at risk for thromboembolism may benefit from aromatase inhibitor therapy (1)[C]. - Taken into account in lumpectomy patients (1)[A] who have received full breast radiotherapy or not. Chemotherapy after surgery is not recommended. Admissions Typically, breast-conserving surgery is performed as an outpatient. Follow-Up For the first five years, a history and physical exam should be performed every six to twelve months, and then just once a year after that. If taking tamoxifen or an aromatase inhibitor, monitor as per NCCN recommendations for lowering the risk of breast cancer. Mammography every 12 months (initial mammography 6 to 12 months following breast conservation therapy). Good prognosis: 10-year breast cancer-specific survival rates of >95%; overall mortality after diagnosis of treated pure DCIS is typically >98%; risk of local recurrence after mastectomy is typically reported as 1-2% (higher in some studies). Following breast-conserving therapy, patients who are younger (especially those under 40 years old), have larger tumors, have higher nuclear grades, and are at higher risk of local recurrences. - Close/positive margin status (associated to DCIS volume) - Comedo-type necrosis The probability of recurrence is decreased in cancers that are ER+. Finding patient subsets with low rates of ipsilateral breast tumor recurrence so they can safely avoid radiotherapy is of interest. - Following breast-conserving surgery, the Oncotype DX DCIS test may aid clinicians in deciding which DCIS patients can safely avoid radiation therapy. The test yields an Oncotype DX DCIS score with the following risk categories: The advantages of radiation therapy are likely to be modest and won't exceed the risks of side effects if the DCIS score is 39, which indicates a low chance of recurrence. Radiation therapy advantages are unknown when compared to the risks of side effects for DCIS scores of 39 to 54. Radiation therapy advantages are probably larger than the risks of side effects in those with DCIS scores of 55 to 100, which indicate a high probability of recurrence.
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