Editing DCIS


Pre-invasive breast malignancy, remaining confined within the ductal system

== Epidemiology ==

* Accounts for 25% of all newly-diagnosed breast cancers

== Risk factors ==

* Essentially the same as for invasive breast cancer

== Pathophysiology ==

* Discrete spaces filled with malignant cells, usually with a recognisable basal cell layer composed of presumably normal myoepithelial cells
* Spreads along the 'galactophoric tree' and often is continuous along the branching ductal network
* The malignant cells can invade across the basement membrane, usually recapitulating the morphology of the cells inside the duct
* Microinvasion - breach of the myoepithelial duct boundary by malignant cells, but measuring <=1mm
** It is possible to mistake various structures for microinvasion, including lobules, crush artefacts, and branching ducts
* 90% of DCIS expresses ER and 40% expresses HER2
** Low-grade lesions have higher ER expression
** Progesterone expression tends to correlate with ER
* Timelines for progression to invasion are not fully understood

== Classification ==

* Grade
** Classify by highest grade present
** Key factors
*** nuclear pleomorphism
*** Nuclear size
*** Nuclear polarity
*** mitotic rate
*** presence of necrosis/calcification
*** solid architecture
** Not as simple as for IDC - can use the NHS Breast Screening Programme (NHS BSP)
*** Low: monomorphic cells, small nuclei, few mitoses, rare necrosis, retained polarity, cribriform or micropapillary architecture
*** Intermediate: moderate pleomorphism, mildly enlarged muclei, polarity largely maintained, solid, cribriform or micropapillary
*** High (60%): nuclear pleomorphism, large nuclei, frequent mitoses, comedo-type necrosis, loss of polarity, frequently solid
* Morphology
** Solid - malignant cells fill extended duct spaces
** Micropapillary - tufts of cells project into the duct lumen perpendicular to the basement membrane
** Papillary - projecting tufts are larger than the microvascular type and contain a fibrovascular core
** Cribriform - the arrangement of malignant cells takes on a fenestrated/sieve-like appearance
** 'Clinging' - single-layered, atypical epithelial cells lining the duct
** Rarer subtypes also exist
* Comedo necrosis presence or absence
** Central necrosis associated with DCIS, although exact definitions vary
** This leads to the microcalcifications
** Central necrosis has a tendency to appear as the cells inside the ductal membrane grow, which coagulates and eventually calcifies, causing the tiny, pleomorphic and frequently linear forms of microcalcifications seen on mammograms

== Presentation ==

* Mostly presents as suspicious calcifications on mammography, often screen-detected
* 80% is impalpable
* Rarely as palpable mass, single-duct nipple discharge or Paget's disease of the nipple
* <1% have metastatic disease
* Multicentric if separate foci of tumours are found in >1 quadrant
* Multifocal if there are separate tumour foci in the same quadrant
* Assessment
** Examine - signs of invasive disease

== Diagnosis ==

* Requires tissue
* Try for core biopsy
* Usually stereotactic, unless there is an associated density
* Clip at same time to aid future localisation
* If impossible, as per breast lump workup, can do surgical excisional biopsy

== Imaging ==

* Mammogram
** Calcifications from necrosis and debris in the involved duct. Tend to cluster together and are pleomorphic.
*** Linear
*** Segmental - branching calcifications extending posteriorly from the nipple into the interior of the breast
** Pleomorphic in size and shape
** 75% have clustered calcifications without an associated density, 15% calcifications and density, and 10% have a density alone
* MRI
** Probably no role if DCIS has already been diagnosed
** Controversial if DCIS has already been diagnosed
** Can be useful in patients where you can't define the extent of disease with standard imaging alone
** Concerns that it overestimates the extent of disease, leading to wider than necessary excisions

== Treatment ==

* Approach
** Prevent development of breast cancer
** Minimise treatment-associated morbidity
** Treatment recommendations based on perceived risk of local recurrence, patient's comorbidities and patient preference
** '''Lumpectomy + radiotherapy +/- tamoxifen is the optimal strategy based on RCTs'''
*** All individually improve recurrence rate
*** About one third of DCIS excisions are found to contain cancer

== Treatment options ==

* Mastectomy
** Indications
*** Patient preference
*** Contraindication to radiotherapy
*** Multicentric or extensive DCIS, or suspected extensive based on mammogram
*** Inability to obtain clear margins with BCS
*** Likelihood of a poor cosmetic result with BCS
*** Unwilling or unable to have follow-up surveillance
*** Recurrence of DCIS after prior treatment with lumpectomy and radiation
** Overtreatment for the majority of patients
** Can be performed in skin-sparing or nipple-sparing fashion if desired
** Does not improve overall survival compared to breast-conserving therapy, but does improve recurrence rate from 1-2% per year to 1-2% lifetime
* Breast-conserving therapy with radiotherapy
** Will require localisation
** Specimen oriented and x-rayed
** Radiation significantly decreases local recurrence risk but does not improve survival
*** Decreased recurrence rate from 30.8% to 14.9%
*** Decreased ipsilateral invasive cancer rate from 16.4% to 7.1%
* Breast-conserving therapy without radiotherapy
** Best for lower-risk cohorts or patient preference
** Proposed low-risk cohort: (however, these results were not validated, and probably still would have a lower risk of recurrence if they had radiotherapy; the effect size is just lower) - note this is low-grade on the Van Nuys prognostic index
*** Low DCIS nuclear grade
*** Small lesion (<1.4cm)
*** Age >60
*** Surgical margins >1cm

== Other treatment considerations ==

* Margins
** Controversial
** >2mm is often considered adequate to declare negative margin - does not significantly increase recurrence rate compared to bigger margins
** <2mm should be considered for re-excision, although >1mm is acceptable in the UK
* SLNB
** Not typically performed with DCIS unless doing a mastectomy
** Indications
*** Microinvasion on core biopsy
*** Otherwise concerning for invasive disease
*** Mastectomy for DCIS (since won't be able to do it later if it's upstaged to invasive on pathology specimen)
*** High-grade, large (>5cm) or palpable DCIS (since there may be a subsequent upstaging based on pathological specimen, which happens about 15% of the time in this cohort)
* Hormone therapy
** If DCIS is ER/PR positive, can give adjuvant hormone therapy for 5 years (either anastrazole or tamoxifen are ok) 
** Benefit only seen with ER-positive DCIS
** Especially important in high-risk patients
** Probably not necessary after mastectomy
** Improves local control after breast-conserving therapy and prevents new tumours
** After 7 years, reduced ipsilateral breast cancer from 9% to 6% and reduced the risk of new contralateral breast cancer by 47%
* Chemotherapy
** Not indicated, as the rate of metastatic disease is so low

== Prognosis ==

* Van Nuys Prognostic Index
** Predicts likelihood of recurrence after BCS for DCIS
** Factors: DCIS size, margin width, pathological assessment (high grade, non-high grade with and without necrosis), age
** Each criterion scored 1-3 and combined
** 4-6 is low, 7-9 is moderate and 10-12 is high risk for 5-year recurrence
** May be able to omit radiotherapy for low-risk disease

* 10 year survival >95%
* Total cancer recurrence rate at 7 years
** 30% with excision alone
** 17% for excision with radiation therapy
** 10% for excision, irradiation, and tamoxifen
* Risk factors for recurrence
** Margins <1mm
** High-grade
** Comedo necrosis
** Age <40yo
** Symptomatic
** ER/PR negative, bcl-2 negative, HER2 positive, p21/p53 positive, high Ki-67

[[Category:Breast]]