1000-2000 5 ьшò

F11.10 Opioid abuse, uncomplicated

F15.10 Other stimulant abuse, uncomplicated

CLINICALPEARLS

Education and PMPs help prevent prescription drug abuse.

Standardized office practice agreements can help manage controlled substance prescriptions.

Asingle effective screening question is “How many times in the past year have you used an illegal drug or prescription medication for nonmedical reasons?”

Discontinue prescription opioid analgesics if pain or functionality does not improve or if there is evidence of abuse (i.e., positive UDS, driving while intoxicated [DWI], accidental or intentional overdose, early refills).

Limit benzodiazepine use to 2 to 4 weeks.

Conduct frequent UDS.

Buprenorphine is an effective treatment for opioid use disorder that can be prescribed by any provider after completing training and obtaining an X waiver. Buprenorphine can also be used to treat chronic pain.

Other medication-assisted treatments for opioid use disorder include naltrexone and methadone (although methadone can only be used to treat opioid use disorder by an addiction specialist).

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DUCTALCARCINOMAIN SITU

Bradley M. Turner, MD, MPH, MHA David G. Hicks, MD

BASICS

DESCRIPTION

Ductal carcinoma in situ (DCIS) is a heterogeneous group of lesions that have in common the presence of a clonal proliferation of neoplastic epithelial cells confined to ducts and lobules.

Considered a premalignant lesion—the neoplastic cells are not invasive (pure DCIS)

Classified as low, intermediate, or high grade

Mortality from DCIS with subsequent progression to invasive breast carcinoma (IBC) is low, regardless of histologic type or type of treatment.

EPIDEMIOLOGY

Incidence

Based on an observed average annual percentage increase of 1%, there were an estimated 61,500 new diagnoses of DCIS in 2017, and there will be an estimated 62,117 new diagnoses of DCIS in 2018.

DCIS accounts for approximately 80–85% of in situ breast carcinomas (lobular carcinoma in situ [LCIS] accounts for approximately 15–20%).

More stable incidence in women 50 to 69 years of age over the last several years

Increasing incidence in women <50 years of age and >70 years of age over the last several years

Represents ~26% of all new IBC

Incidence rate of DCIS is comparable among women of different ethnicities.

ETIOLOGYAND PATHOPHYSIOLOGY

Anonobligate precursor to IBC

Presumed to be the final step prior to IBC, part of a poorly understood spectrum of polyclonal and clonal epithelial proliferative lesions

Either lowor high-grade DCIS has the potential for subsequent invasion into

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the surrounding stroma; however, the changes necessary for transition to IBC are poorly understood.

Molecular evidence suggests that lowand high-grade DCIS are genetically distinct lesions, with high-grade DCIS associated with more aggressive disease.

Genetics

typically shows diffuse and strong expression of without HER2 protein

mutations

overexpression is even more frequent in high-grade DCIS compared to IBC.

associations observed; only screen those at high risk.

RISK FACTORS

Female gender, nulliparity, late age at first birth, late age at menopause, family history of a first-degree relative with breast cancer,

replacement therapy (combined estrogen/progestin),

Association with age, body mass index, smoking, lactation, early menarche, increased

GENERALPREVENTION

Screening increases overdiagnosis with little or no reduction in the incidence of advanced cancers.

Women with increased risk should have more aggressive screening (risk assessment tool available at http://www.cancer.gov/bcrisktool/Default.aspx). General screening guidelines—U.S. Preventive Services Task Force (USPSTF):

–Biennial mammography for women aged 50 to 74 years (B recommendation)

–Mammography prior to age 50 years should be patient centered.

–Biennial screening of ages 40 and 49 years without evidence of benefit (C recommendation)

–Insufficient evidence to support screening mammography in women aged

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75 years or older

–There is insufficient evidence to assess the benefits and harms of digital breast tomosynthesis (DBT) as a primary screening method for breast cancer (I statement).

–Insufficient evidence to support adjunctive screening for breast cancer using breast ultrasonography, magnetic resonance imaging (MRI), DBT, or other

methods in women with dense breasts on an otherwise negative screening mammogram (I statement)

General screening guidelines—National Comprehensive Cancer Network (NCCN):

–NCCN recommends that women should be familiar with their breast; promptly report changes to their health care provider; and that periodic, consistent BSE may facilitate breast self-awareness.

–Ages 25 to 39 years: breast awareness, CBE every 1 to 3 years

–Age 40 years and older: breast awareness, annual CBE, annual screening

mammography

If no intervention would occur based on screening findings, patient should not undergo screening.

Risk reduction:

–Lifestyle modifications: Limit alcohol to <1 drink/day, exercise, maintain healthy diet, BMI <30.

–Hormonal agents (i.e., tamoxifen) are recommended in certain high-risk women ≥35 years of age; benefits of aromatase inhibitors are less clear.

–Arecent clinical trial with (an aromatase inhibitor) showed a significantly decreased incidence of DCIS in postmenopausal women.

DIAGNOSIS

HISTORY

Most DCIS is now diagnosed by screening mammography (presence of

in approximately 72%); patients may be asymptomatic with nonpalpable mass (12%) (1,2)[A].

Advanced lesions may present with a palpable mass, nipple discharge, or Paget disease (1)[A].

PHYSICALEXAM

CBE with inspection of breasts with patient in upright and supine position;

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evaluating for asymmetry, spontaneous discharge, skin changes (peau d’orange, erythema, scaling); nipple retraction/excoriation (Paget disease) Palpation of all breast quadrants with patient in upright and supine position, including lymph node examination (axillary, supraclavicular, and internal

mammary nodes)

Positive clinical findings: Refer for consideration of diagnostic imaging and/or surgical evaluation unless <30 years of age with a low clinical suspicion (observe 1 to 2 menstrual cycles; if positive clinical findings persist, refer for imaging).

DIFFERENTIALDIAGNOSIS

Usual ductal hyperplasia, flat epithelial atypia, ADH, LCIS, microinvasive carcinoma (1)[A]

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

Mammography Breast Imaging Reporting and Data System (BI-RADS) developed by the American College of Radiology is used for uniform reporting of mammography results.

BI-RADS interpretation: categories (0 to 6) 0: incomplete and needs additional imaging; 1: negative; 2: benign finding; 3: probably benign finding; 4: suspicious abnormality; 5: highly suggestive of malignancy; 6: known biopsy-proven malignancy

Similar BI-RADS interpretations for diagnostic ultrasound (US)

Screening BI-RADS category 0: diagnostic workup with consideration for diagnostic imaging

Screening BI-RADS categories 1 and 2: screening recommendations

Screening BI-RADS category 3: diagnostic imaging at 6 months and then every 6 to 12 months for 2 to 3 years; consider biopsy if patient anxious or follow-up uncertain.

Screening BI-RADS categories 4 and 5: diagnostic imaging with follow-up

Screening BI-RADS category 6: technically not a “screening” category other than to assess a known cancer that might need additional evaluation. NCCN guidelines for breast cancer should be followed.

DCIS is commonly seen on imaging as clustered microcalcifications (2)[A].

Diagnostic imaging will result in consideration for tissue biopsy.

Follow-Up Tests & Special Considerations

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US not recommended for screening

The sensitivity of breast MRI screening is higher than mammography but has lower specificity resulting in a greater number of false positives (2)[A].

Screening with MRI as an adjunct to screening mammogram is only recommended in certain women: BRCA mutation (commence at age 25 to 29 years) (3)[A]; first-degree relative of BRCA carrier (commence at age 25 to 29 years) (3)[A]; ≥20% lifetime risk of breast cancer, defined by models that are largely based on family history (3)[A]; radiation to chest between the ages of 10 and 30 years (3)[C]; presence of Li-Fraumeni, PTEN, or Bannayan-Riley- Ruvalcaba syndrome in patient or first-degree relative (3)[C]; ≥20% risk of breast cancer based on geneand/or risk-level ATM, CDH1, CHEK2, PALB2, PTEN, STK11, TP53 (3)[C].

There is insufficient evidence to recommend for or against MRI screening in the following groups: 15–20% lifetime risk of breast cancer, defined by models that are largely based on family history; heterogeneous or extremely dense breast tissue on mammography; personal history of breast cancer or DCIS.

Screening with MRI is not recommended in women with <15% lifetime risk of breast cancer (3)[C]. MRI can also complement mammography in patients with skin changes.

Although MRI and US are complementary diagnostic methods to mammography, US is less sensitive in detecting most microcalcifications and MRI does not typically detect microcalcifications at all (2)[A].

After a diagnosis of DCIS, MRI has been prospectively shown to have a sensitivity of up to 98% for high-grade DCIS (4)[A].

The NCCN Panel has included breast MRI as indicated during the initial workup of DCIS, noting that the use of MRI has not been shown to increase the likelihood of negative margins or decrease the conversion to mastectomy with DCIS.

Pathology

–Tissue is necessary for diagnosis: core needle (CN) or vacuum-assisted (VA) biopsy (mammographic/stereotactic, US, or MRI guided). Open surgical biopsy for those not amenable to CN or VAbiopsy.

–Fine-needle aspiration (FNA) is not adequate for specific diagnosis of DCIS.

–Histologic classification

Classification is subjective; however, traditionally classified as either low, intermediate, or high grade based on architectural patterns (comedo, solid, cribriform, clinging, papillary, and micropapillary), nuclear grade

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(I, II, or III), and the absence or presence of necrosis (1,2).

Ductal intraepithelial neoplasia (DIN) is an alternative histologic classification incorporating size as a discriminating factor (2)[C].

Grade is more important for prognosis, risk for progression, and local recurrence.

Comedo-type necrosis (necrosis filling central portion of involved duct) is typically seen in high-grade DCIS, with varying degrees of necrosis in other types of DCIS.

–Determination of ER and PR status (1,4)[A]

–Studies show unclear or weak evidence of HER2 status as a prognostic indicator in DCIS.

TREATMENT

SURGERY/OTHER PROCEDURES

Surgery is the primary treatment option. Options for surgery are based on risk of recurrence, anatomic location, extent of disease, and the ability to achieve “negative” margins (4)[A].

Positive margins are considered “ink on tumor.”

Totality of evidence does not support the routine practice of obtaining negative margin widths wider than 2 mm (4)[C],(5)[A].

Margins <1 mm considered inadequate (1,4,5)[A]

Margins <1 mm at the breast fibroglandular boundary (chest wall or skin) do not mandate surgical excision but may be an indication for higher boost dose radiation in patients opting for breast conservation (4)[A].

DCIS with microinvasion, defined as no invasive focus >1 mm in size, should be considered as DCIS when considering the optimal margin width (4)[C]. When there is only minimal or focal DCIS involvement near the margin, clinical judgment can be applied to determine if reexcision might be avoided in individual cases(4)[C].

Surgical options include the following:

–Breast conservation (lumpectomy) without lymph node procedure, without breast radiation therapy (4)[A]

–Breast conservation (lumpectomy) without lymph node procedure, with whole breast radiation therapy, with or without boost to tumor bed (4)[A]

–Acomplete axillary lymph node dissection should not be performed in the absence of evidence of invasive cancer or proven axillary metastatic disease

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(4)[A].

–Asentinel lymph node biopsy may be considered if the lumpectomy is in an anatomic location compromising the performance of a future sentinel lymph node procedure (4)[C].

–Radiation decreases recurrence rates by about 50% (2)[A].

–~50% of recurrences are pure DCIS; ~50% are IBC (1,4)[A].

–Drawbacks to radiation therapy include (i) the patient’s burden of daily treatment for 6 weeks and short-term side effects, such as fatigue and skin toxicity; (ii) a slightly increased risk of secondary cancers; and (iii) inability to receive radiation therapy again in the ipsilateral breast should an invasive carcinoma develop.

–Recurrence generally requires mastectomy with consideration for systemic treatment (2)[C].

–Patients not amenable to margin-free lumpectomy should have total mastectomy (4)[C].

–Mastectomy with or without sentinel node biopsy plus optional breast reconstruction (4)[A]

–Mastectomy provides maximum local control.

–Rates of recurrence for DCIS and IBC are similar to lumpectomy.

–Recurrence should be treated with wide local excision, chest wall radiation, and consideration for systemic treatment (4)[A].

–Long-term cause-specific survival seems to be equivalent to lumpectomy with whole breast radiation (4)[A].

–Asentinel lymph node biopsy may also be considered in patients with seemingly pure DCIS to be treated with mastectomy (4)[C].

Secondary chemoprevention following breast-conserving surgery for ER + DCIS:

–Tamoxifen for premenopausal patients or tamoxifen or an aromatase inhibitor for postmenopausal patients for 5 years (3)[A]

–There may be some advantage for aromatase inhibitor therapy in patients <60 years old or patients with concerns for thromboembolism (4)[C].

–Considered in lumpectomy patients with or without whole breast radiation (4)[A]

–Benefit of tamoxifen and trastuzumab in ER-negative/HER2-positive disease is unclear (1)[C].

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ONGOING CARE

FOLLOW-UPRECOMMENDATIONS

History and physical exam every 6 to 12 months for the first 5 years and then annually

Mammography every 12 months (first mammogram 6 to 12 months after breast conservation therapy) (4)[C]

If treated with tamoxifen or an aromatase inhibitor, monitor per NCCN guidelines for breast cancer risk reduction (4)[C].

PROGNOSIS

Good prognosis: 10-year breast cancer–specific survival rates of >95%; overall mortality after diagnosis of treated pure DCIS generally >98%

Risk of local recurrence after mastectomy generally reported as 1–2% (higher in some studies)

Higher risk of local recurrences after breast-conserving therapy in younger age (particularly before age 40 years), larger tumor size, high nuclear grade, comedo-type necrosis, and close/positive margin status (related to DCIS volume)

ER+ tumors are associated with lower risk for recurrence.

The Oncotype Dx DCIS score, a multigene assay including seven DCISrelated genes, offers hope for quantifying the risk of local recurrence of DCIS or the development of IBC in patients treated with breast-conserving therapy alone.

REFERENCES

1.Siziopikou KP. Ductal carcinoma in situ of the breast: current concepts and future directions. Arch Pathol Lab Med. 2013;137(4):462–466.

2.Lee RJ, Vallow LA, McLaughlin SA, et al. Ductal carcinoma in situ of the breast. Int J Surg Oncol. 2012;2012:123549.

3.NCCN clinical practice guidelines in oncology: breast cancer screening and diagnosis (Version 1.2017) 2017. National Comprehensive Cancer Network Web site. http://www.nccn.org. Accessed on November 13, 2017.

4.NCCN clinical practice guidelines in oncology: breast cancer (Version 3.2017) 2017. National Comprehensive Cancer Network Web site. http://www.nccn.org. Accessed on November 13, 2017.

5.Morrow M, Van Zee KJ, Solin LJ, et al. Society of Surgical Oncology-

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American Society for Radiation Oncology-American Society of Clinical

Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in ductal carcinoma in situ. J Clin Oncol. 2016;34(33):4040–4046.

ADDITIONALREADING

Gøtzsche PC, Jørgensen KJ. Screening for breast cancer with mammography.

Cochrane Database Syst Rev. 2013;(6):CD001877.

NCCN clinical practice guidelines in oncology: breast cancer risk reduction (Version 1.2017) 2016. National Comprehensive Cancer Network Web site. http://www.nccn.org. Accessed on November 13, 2017.

Siu AL; for U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventative Services Task Force recommendation statement. Ann Intern Med. 2016;164(4):279–296.

SEE ALSO

Breast Cancer

CODES

ICD10

D05.10 Intraductal carcinoma in situ of unspecified breast

D05.11 Intraductal carcinoma in situ of right breast D05.12 Intraductal carcinoma in situ of left breast

CLINICALPEARLS

DCIS is a heterogeneous group of noninvasive neoplastic lesions from breast ductal epithelial cells.

The incidence of DCIS has increased in women <50 and >70 years.

The goal of DCIS treatment is to prevent recurrence and progression to IBC.

Current standard of care: breast-conserving therapy with consideration for postoperative whole-breast radiation therapy and/or postsurgical tamoxifen or aromatase inhibitor therapy

With appropriate therapy, the overall prognosis of pure DCIS is good.

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