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• TP53 is a tumor suppressor gene:
  • That plays a crucial role in:
    • Maintaining genomic stability and regulating cell cycle checkpoints
• Carriers of a TP53 pathogenic variant:
  • Would be expected to be unable to repair tissue damage from DNA-damaging radiotherapy and be at risk for significant radiotherapy-associated sequelae
• Outcomes reported in published case reports:
  • Support this recommendation against radiotherapy in women with breast cancer who are carriers of a TP53 pathogenic variants:
    • Due to increased risk of radiation-induced secondary malignancies
• Mutations in TP53 are considered:
  • An absolute contraindication of radiotherapy:
    • Except in those with a significantly high risk of locoregional recurrence
  • Mastectomy is the recommended therapeutic surgical option
• The radiotherapy-induced toxicity spectrum in patients with breast cancer carrying ATM pathogenic variants is controversial:
  • Seven studies identified in a systematic review addressed radiotherapy after breast-conserving surgery among women with breast cancer who harbor ATM pathogenic variants:
    • Meyer et al found no significant differences in local relapse-free survival in a cohort of 138 patients with early stage breast cancer treated with breast-conserving surgery, followed by radiotherapy, of whom 20 were found to carry either an ATM truncating or missense variant:
      • They concluded that the results do not support the hypothesis that patients with breast cancer carrying a sequence variant in the ATM gene differentially benefit from postoperative radiotherapy
• According to the ASCO-ASTRO-SSO Consensus recommendations for carriers of BRCA 1/2 and other germline pathogenic variants,:
  • Women with breast cancer may safely be offered radiotherapy when clinically indicated
  • Data on toxicity rates comparing carriers of ATM pathogenic variants and noncarriers:
    • Do not favor avoiding radiotherapy:
      • Potential absolute risks do not appear to be significant:
        • However, more research is needed
  • A discussion with ATM carriers interested in breast-conserving therapy is encouraged
  • There is no evidence of increased toxicity or contralateral breast cancer events from radiation exposure in BRCA 1/2, CHEK2, CDH1 carriers
• References:
  • Trombetta MG, Dragun A, Mayr NA, Pierce LJ. ASTRO Radiation Therapy Summary of the ASCO-ASTRO-SSO Guideline on Management of Hereditary Breast Cancer. Pract Radiat Oncol. 2020;10:235-242.
  • Lazzari G, Buono G, Zannino B, Silvano G. Breast cancer adjuvant radiotherapy in BRCA1/2, TP53, ATM genes mutations: Are there solved issues? Breast Cancer (Dove Med Press). 2021;13:299-310.
  • Ferrarini A, Auteri-Kaczmarek A, Pica A, et al. Early occurrence of lung adenocarcinoma and breast cancer after radiotherapy of a chest wall sarcoma in a patient with a de novo germline mutation in TP53. Fam Cancer. 2011;10:187-192.
  • Heymann S, Delaloge S, Rahal A, et al. Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li- Fraumeni syndrome. Radiat Oncol. 2010;5:104.
  • Meyer A, John E, Dörk T, Sohn C, Karstens JH, Bremer M. Breast cancer in female carriers of ATM gene alterations: outcome of adjuvant radiotherapy. Radiother Oncol. 2004;72: 319-323.

• Bioactive free T4 concentrations:
  • Can be estimated using a variety of indirect (analog, immunometric, and two-step labeled hormone assays) or direct methods (equilibrium dialysis, ultrafiltration), and are the most commonly used measurements of circulating thyroid hormone levels
• Generally, most laboratories estimate free T4 by either the analog immunoassay or a calculated FT4I corrected to thyroid hormone binding capacity:
  • The former is readily available and provides quick results; it does not directly measure the free T4 concentration but is a reliable estimate of FT4 levels in most patients, based on one-step, two-step, or labeled antibody approaches
• This type of free T4 estimate is especially sensitive to abnormal serum albumin levels and should not be used with conditions such as:
  • Familial dysalbuminemic hyperthyroxinemia, pregnancy, or severe nonthyroidal illness:
    • For example, it is common to have a free T4 lower than the reference range in a euthyroid pregnant woman:
      • Due to the high estrogen state of pregnancy greatly increasing serum TBG concentrations, thus resulting in inaccurate FT4 measurements
• The serum FT4I measurement is a calculated value that is the product of the total T4 concentrations and a correction factor related to the number of available thyroid hormone binding sites:
  • This correction factor may be called:
    • A thyroid hormone binding ratio (THBR), T3 resin uptake (T3RU), or T3 uptake (T3U)
    • The T3RU is inversely related to the free thyroid hormone binding sites but is now used in only a few laboratories
• Free T4 by equilibrium dialysis:
  • Is the gold standard and measures the 0.03% of T4 that is biologically active and unbound to protein
  • This assay is available only at reference laboratories and is useful to directly determine free T4 levels when other testing does not provide a clear result
• Although a TSH-first testing algorithm is suffcient for general screening:
  • Both FT4 and TSH assays are needed for:
    • Diagnosing subclinical thyroid dysfunction, central hypothyroidism, and in the assessment of elderly and hospitalized patients, as well as for accurate assessment of treatment effects
• Guidelines from multiple thyroid and endocrine societies:
  • Have also endorsed a TSH-first strategy in most clinical scenarios with FT4 testing when clinically indicated or TSH is found to be abnormal
  • Work by Henze et al. goes even further suggesting that a TSH-first strategy can be further perfected by:
    • Widening the TSH reference range from 0.4 to 4.0 mIU/L to 0.2–6.0 mIU/L with minimal impact on case detection
    • They found that only 4.2% of TSH values between 0.2 mIU/L and 0.4 mIU/L would not have led to detection of a high FT4 and equally, only 2.5% of TSH values between 4.0 mIU/L and 6.0 mIU/L were associated with low FT4 level
    • It is likely that this small additional group of patients outside the wider range with abnormal FT4 is clinically unimportant in most cases

• Serum total T4 (TT4) and total T3 (TT3) concentrations:
  • Are a measure of both the bound and free hormone levels of these two hormones
• TT4 or TT3 levels should be interpreted in the context of the clinical situation:
  • Because many clinical conditions and medications alter the concentrations of thyroid hormone binding proteins and / or compete with the binding of thyroid hormones to the binding proteins:
    • As such, measured TT4 and TT3 levels may be affected, even though the bioactive free levels and thus, the thyroidal status, remain unchanged
• T3 is the active thyroid hormone:
  • It is primarily useful in the diagnosis and management of patients with hyperthyroidism
  • It occasionally can be used to differentiate stimulation induced thyrotoxicosis / Graves’ disease (TT3 / TT4 ratio > 20) from destruction induced thyrotoxicosis / subacute thyroiditis (TT3 / TT4 ratio < 12):
    • This assessment can be further augmented when TSH is considered as serum levels of TSH are generally suppressed in most untreated Graves’ patients, whereas they usually were not completely suppressed in patients with painless thyroiditis or subacute thyroiditis
  • Measurement of serum TT3 is not usually helpful if hypothyroidism is suspected:
    • Because the activity of 5’deiodinas type 2 enzyme (Dio2):
      • Which converts T4 to the biologically active T3:
        • Increases while serum T4 falls:
          • Thus maintaining normal T3 levels until the overall thyroid hormone levels are very low
• rT3, which may be elevated during nonthyroidal illness:
  • Is not biologically active:
    • As such, the utility of measuring it and other forms of inactive iodothyronine are limited during the evaluation of thyroid status
• Finally, the human anti-mouse antibodies (HAMAs) that interfere with TSH testing:
  • Can also interfere with the thyroid hormone assays
  • HAMA positivity:
    • May result in artificially elevated or reduced TT4, TT3, FT4, and FT3 levels
  • Patients who have received therapeutic monoclonal antibody treatment may be at increased risk of develop interfering positive HAMA titers

• Thyroid Stimulating Hormone (TSH):
  • Is produced from the anterior pituitary gland:
    • After stimulation by thyrotropin-releasing hormone (TRH)
• Thyrotropin-releasing hormone (TRH):
  • Is a modified three-amino acid peptide:
    • Produced by neurons of the paraventricular nucleus:
      • In the hypothalamus
  • TRH signaling from the hypothalamus:
    • Is achieved through a portal venous system:
      • Located in the infundibulum of the pituitary stalk:
        • Which allows communication to the pituitary gland
• Both TRH and TSH gene expression:
  • Are decreased by excess thyroid hormone levels:
    • Via negative feedback mechanisms (Figure)
  • Both the hypothalamus and pituitary:
    • Have high levels of 5′deiodinases Type 2 enzyme (Dio2):
      • Catalyzes the removal of the 5′ iodine from the outer ring of thyroxine (T4):
        • To create the metabolically active triiodothyronine (T3)
      • So T4 levels are the primary feedback:
        • T4 is converted locally to T3:
          • Which suppresses TRH and TSH gene expression

• Pituitary TSH is secreted in a pulsatile manner:
  • Higher levels at night and lower levels during the day:
    • The inverse of the cortisol cycle
  • Although pulse frequency is increased nocturnally to result in a diurnal variation of TSH concentrations:
    • Levels remain within the reference range
  • Generally, laboratory testing of serum TSH concentrations during daylight hours:
    • Is not substantially affected by the diurnal variation of TSH secretion:
      • But results outside the reference range may occur in euthyroid individuals when drawn outside of these times
• TSH stimulates the synthesis and release of thyroid hormone from the thyroid gland:
  • TSH production from the anterior pituitary gland is inverse log-linearly regulated by serum thyroid hormone concentrations:
    • When there are small decreases in thyroid hormone levels in circulation:
      • Large increases in serum TSH stimulate thyroid hormone production by the thyroid gland
    • This negative feedback loop between serum TSH and the serum-free thyroid hormones:
      • Is able to maintain circulating thyroid levels within a tight range
• Serum TSH is the preferred screening test:
  • In the evaluation of thyroid function in the ambulatory patient:
    • Regardless of whether the patient is taking thyroid hormone replacement medication
• For the healthy patient in an ambulatory setting:
• The diagnosis of hypothyroidism or hyperthyroidism:
  • May be determined with approximately 98% sensitivity and 92% specificity using serum TSH
  • In addition, TSH has a narrow intraindividual variability of ± 0.5 mIU/L:
    • Such that thyroid dysfunction may be present if there are significant changes in TSH values over time in an individual, even if they remain within the reference range
• In certain situations, however, such as known or suspected pituitary or hypothalamic dysfunction, recent hyperthyroidism, critical illness, starvation, use of certain medications (dopamine or high-dose glucocorticoids), interference with serum thyroid autoantibodies, and thyroid hormone resistance syndromes:
  • The TSH level is inaccurate for the thyroidal status and should not be used in isolation to determine thyroid function
• In addition, the presence of interfering heterophile antibodies (antibodies against the animal-derived antibodies used in the immunometric assay):
  • May rarely cause abnormally high or low TSH levels:
    • These conditions should be suspected when the pattern of the TSH levels does not correlate to the clinical presentation or when the peripheral serum hormone levels do not change as expected with elevated or suppressed serum TSH concentrations
• Serum TSH assays:
  • Have evolved considerably since measurements were first described in the 1960s:
    • When the functional sensitivity was between 1 and 2 mIU/L
  • The commonly used second-generation TSH assays have an improved functional lower limit of 0.10 to 0.20 mIU/L:
    • Which is able to differentiate between euthyroid and hyperthyroid states but does not indicate the degree of hyperthyroidism
  • In contrast, a third-generation TSH assay can detect levels as low as 0.01 to 0.02 mIU/L:
    • This is helpful when there is a challenging pattern of serum thyroid function tests that include an extremely suppressed TSH
  • In the rare instance they are needed, fourth-generation immunochemiluminometric assays are capable of detecting TSH levels in the range of 0.01 to 0.001 mIU/L
• A serum TSH level measured in an ambulatory population that lies within the reference range:
  • Is generally considered evidence of normal thyroid function and requires no additional testing
  • Reference ranges for serum TSH can vary slightly from one commercial laboratory to another:
    • It should be noted that normal ranges, which are based on the epidemiologic distribution of serum TSH concentrations in healthy populations:
      • From which serum thyroid autoantibody positivity and iodine status (both of which can affect TSH), may be variable
  • If an abnormal screening TSH result is encountered:
    • The circulating thyroid hormone levels should be assessed
      • The specific pattern of tests will allow further insight into whether clinical thyroid dysfunction should be suspected

• Hyperthyroidism and hypothyroidism:
  • Are often the result of autoimmune diseases:
    • In which immunoglobulin G (IgG) antibodies:
      • Such as thyroid peroxidase (TPO Ab, previously known as antimicrosomal antibodies), thyroglobulin (Tg Ab), and the TSH receptor (TSHR Ab):
        • Are formed against thyroid proteins
  • The presence of TPOab is commonly associated with patients with hypothyroidism:
    • But can be present in normal individuals who do not display any obvious symptoms of clinical thyroid disease
  • TPOabs are present in approximately 10% of normal individuals:
    • While it was detected in almost 100% of samples of patients with autoimmune hypothyroidism
• More than 90% of patients with autoimmune thyroid disease (Hashimoto’s thyroiditis and Graves’ disease):
  • Will have elevated titers of second-generation assays for TPO Ab and Tg Ab
• When biochemical hypothyroidism is found:
  • Measuring TPO Ab can be helpful:
    • Because its result can provide additional information regarding the etiology of the thyroid dysfunction
• Median serum TSH concentrations are increased within the reference range:
  • Among those with serum TPO Ab and Tg Ab positivity:
    • Compared with those without TPO Ab titers, and are a predictor for the development of biochemical thyroid dysfunction in euthyroid individuals
• In individuals with subclinical hypothyroidism:
  • Both serum TPO Ab positivity and sonographic characteristics suggestive of chronic thyroiditis:
    • Are associated with an increased likelihood of progression to overt hypothyroidism
• The TSHR Abs are a group of immunoglobulins:
  • That produce Graves’ hyperthyroidism
  • Measured as:
    • TSH receptor binding, TRAB (TSH-receptor antibody) or in a functional bioassay, thyroid stimulating immunoglobulin (TSI)
  • TSH receptor antibodies:
    • Are being increasingly recommended for monitoring activity of disease to assess response to therapy in Graves’ patients
  • Less commonly, TSH receptor binding antibodies:
    • Can block the TSH receptor and produce hypothyroidism
• In the setting of normal serum thyroid function:
  • Thyroid antibodies should generally not be measured except in special circumstances:
    • Such as a history of hyperthyroidism during pregnancy or recurrent miscarriages:
      • In these situations, both the stimulating and inhibiting TSHR Abs can cross the placenta to affect fetal thyroid function and potentially induce fetal goiter
    • Although serum thyroid antibody positivity during pregnancy:
      • Is associated with a higher risk of postpartum subacute thyroiditis:
        • Antibody screening in pregnant women is not currently recommended

• The evaluation of a chronically ill or hospitalized patient with abnormal serum thyroid function tests:
  • Can often be challenging
• Nonthyroidal illness is not considered a primary thyroid disorder:
  • Its pathophysiology is not completely understood:
    • Although it is known that the elevation of cytokines and hypoxia plays a significant role
  • It is generally recommended to avoid measuring serum thyroid function tests during acute illness:
    • Unless thyroid dysfunction is thought to be a significant contributor to the illness
• Severe nonthyroidal illness:
  • Is accompanied by significant alterations in thyroid physiology
• Due to the decreased availability in all of the thyroid binding proteins (thyroxine bindings globulin, transthyretin, albumin):
  • Serum total T4 and total T3 levels are reduced:
    • Whereas free levels are usually normal or slightly low (Figure)
  • Total T3 levels are further decreased:
    • Due to reduced Dio1 activity:
      • Which converts T4 to T3
  • A relatively greater amount of T4 is metabolized to the inactive metabolite:
    • Reverse T3 (rT3):
      • By Dio3
    • Although measurement of rT3 does not reliably distinguish nonthyroidal illness from primary hypothyroidism
    • The degree of serum rT3 elevation, depressed T3 / rT3 ratio, and decreased FT3 and FT4 concentrations:
      • Have been associated with higher mortality among patients in the intensive care unit (ICU):
        • Treatment with T4 or T3, however, does not consistently improve outcome
    • Whether other T4 metabolites, including 3,3′-diiodothyronine (3,3′-T2); 3,5-diiodothyronine (3,5-T2); and 3-iodothyronamine (3-T1AM):
      • Have functional roles in nonthyroidal illness remains unclear

• It is important that the diagnosis of primary thyroid dysfunction:
  • Is not established during severe illness based solely on an abnormal serum TSH
• In nonthyroidal illness:
  • Serum TSH concentrations may be low, normal, or high:
    • Due to the TSH-lowering effects of commonly used medications (glucocorticoids, ipodate, amiodarone, dopamine) in patients managed for a nonthyroidal illness or from a reversible form of acquired central hypothyroidism in severe nonthyroidal illness
• During the recovery phase of nonthyroidal illness:
  • The TSH may briefly rise above the upper reference range, as suppression of TSH lessens, before it normalizes
  • When possible, thyroid evaluation after recovery from an acute illness is recommended in patients suspected of having intrinsic thyroid disease

• Fine linear or branching calcifications:
  • In a group or segmental distribution:
    • Are often associated with high-grade DCIS
• Amorphous calcifications:
  • Are often associated with low-grade DCIS
• Mammography relies on the presence of calcifications for the detection of DCIS:
  • Thus, lesions without calcifications are generally occult on mammography
• Extensive DCIS:
  • Can present as a palpable mass
• Nipple discharge:
  • Can also be a sign of either DCIS or invasive breast cancer
• Paget disease:
  • Is a rare presentation:
    • Occurring in only 1% to 4% of women with breast cancer
  • It is characterized histologically by:
    • Intraepithelial tumor cells
    • It presents as a chronic ulceration or eczema of the nipple:
      • That can involve the surrounding areolar skin
  • It may be associated with invasion but, in the absence of invasion:
    • Is treated as DCIS

#Arrangoiz #CancerSurgeon #BreastSurgeon #SurgicalOncologist #BreastCancer #LCIS #DCIS #DuctalCarcinomaInsitu #LobularNeoplasia #LobularCarcinomaInsitu #Surgeon #Teacher #Miami #Mexico #MSMC #MountSinaiMedicalCenter

• Pure ductal carcinoma in situ (DCIS):
  • Is by definition non-invasive:
    • Thus lacks the ability to metastasize to axillary nodes and distant sites:
    • For this reason, surgical axillary staging is not recommended in the management of most patients with DCIS undergoing breast conserving surgery
• Approximately 20% of patients with DCIS on core needle biopsy:
  • Will upstage to invasive cancer:
    • And may ultimately require surgical axillary staging
• Factors associated with upstaging to invasive disease include:
  • A palpable mass at the time of diagnosis
  • Intermediate- or high-grade lesions
  • Comedonecrosis
  • ER negative (-) subtype
  • A large span of disease:
    • Typically cited as > 5cm
• The location of the lesion (eg. upper outer quadrant):
  • Is not predictive of upgrade or spread to regional / distant sites
• While some authors cite multifocality as a risk factor for upstaging:
  • It is more predictive of recurrence than upstage
• One exception to the recommendation of omission of SLNB is:
  • For DCIS patients undergoing mastectomy:
    • First, most patients undergoing mastectomy for DCIS have a larger burden of disease:
      • Therefore have a higher likelihood of upstaging to invasive cancer:
        • For which surgical axillary staging is warranted
    • Second, while axillary mapping and sentinel lymphadenectomy may be feasible after mastectomy (with injection of radiocolloid and / or blue dye into the remaining skin):
      • The accuracy of this strategy has not been fully evaluated and is therefore not the recommended approach
    • However, since the rate of nodal positivity is low in these patients, newer strategies (such as injection of superparamagnetic iron oxide nanoparticles at time of mastectomy as a tracer for delayed sentinel lymph node dissection):
      • Are under investigation and may serve to decrease the number of patients with DCIS undergoing surgical axillary staging
• References:
  • American Society of Breast Surgeons. Consensus Statement on Axillary Management for Patients With In-Situ and Invasive Breast Cancer: A Concise Overview.
  • Lee, S.K., et al. Nomogram for predicting invasion in patients with a preoperative diagnosis of ductal carcinoma in situ of the breast. British J Surg. 2013;100: 1756-1763.
  • Tanaka, K., et al. Clinicopathological predictors of postoperative upstaging to invasive ductal carcinoma (IDC) in patients preoperatively diagnosed with ductal carcinoma in situ (DCIS): a multi-institutional retrospective cohort study. Breast Cancer. 2021;28: 896–903.
  • Salvatorelli, L., et al. Ductal Carcinoma In Situ of the Breast: An Update with Emphasis on Radiological and Morphological Features as Predictive Prognostic Factors. Cancers. 2020; 12(3), 609.
  • Port, E.R., et al. Reoperative sentinel lymph node biopsy: a new frontier in the management of ipsilateral breast tumor recurrence. Ann Surg Oncol. 2007;14(8):2209–14.
  • Karakatsanis, A., et al. Delayed Sentinel Lymph Node Dissection in Patients with a Preoperative Diagnosis of Ductal Cancer In Situ by Preoperative Injection with Superparamagnetic Iron Oxide (SPIO) Nanoparticles: The SentiNot Study. Ann Surg Oncol. 2023;30:4064-4072
• Due to the non-invasive nature of ductal carcinoma in situ (DCIS):
  • Assessment of the axilla is not indicated regardless of receptor status or grade with pure DCIS in the setting of breast conserving surgery
• It may be considered if the patient is undergoing a mastectomy or the tumor is located in a position where excision may compromise future performance of a sentinel lymph node biopsy
• Microinvasive DCIS:
  • Comprises 5% to 10% of all cases of DCIS
  • In a review of the literature, the reported incidence of axillary metastases in microinvasive DCIS:
    • Has ranged from 0% to 28%
  • Axillary staging is appropriate and sentinel node biopsy should be performed in the setting of microinvasive DCIS
• References
  • NCCN Guidelines 2023.  breast.pdf (nccn.org)  Last accessed 9/24/23.
  • Consensus Statement on Axillary Management for Patients with In-Situ and Invasive:  A Concise Overview.  Official Statements | ASBrS (breastsurgeons.org)  Last accessed 10/9/23
  • Adamovich TL, Simmons RM. Ductal carcinoma in situ with microinvasion. Am J Surg 2003; 186: 112–6.
  • Guth AA, Mercado C.  Microinvasive breast cancer and the role of sentinel node biopsy:  an institutional experience and review of the literature.  Breast J.  2008; 14 (4); 335-9.

• The eighth edition of the American Joint Committee on Cancer (AJCC) staging system:
  • Defines microinvasion as invasion of breast cancer cells through the basement membrane:
    • At one or more foci:
      • None of which exceeds a dimension of 1 mm
• DCIS:
  • Is a Tis lesion:
    • It is classified as stage 0 cancer
• DCIS with microinvasion:
  • Is considered T1mi:
    • It upstages DCIS from stage 0 to stage I disease
• By definition, DCIS without microinvasion:
  • Does not have the ability to metastasize to axillary lymph nodes or distant sites:
    • Whereas DCIS with microinvasion does
• Axillary metastases:
  • Have been reported in 0% to 20% of patients:
    • With DCIS with microinvasion
• The incidence of microinvasion in DCIS:
  • Varies according to the size and extent of the index lesion
• Lagios et al. reported:
  • A 2% incidence of microinvasion in patients with DCIS measuring less than 25 mm in diameter:
    • Compared with a 29% incidence of microinvasion in those with lesions larger than 26 mm
• The incidence of microinvasion is also higher:
  • In patients with high-grade or comedo-type DCIS with necrosis
  • In patients with DCIS who present with a palpable mass or nipple discharge
• There is conflicting data in the literature on the prognosis of DCIS with microinvasion compared to DCIS without microinvasion:
  • Historically, studies have shown that patients with DCIS with microinvasion have a worse prognosis compared with those who have DCIS alone
  • In a retrospective study of 1,248 serially sectioned DCIS tumors, de Mascarel et al:
    • Reported a 10.1% incidence of axillary metastases in cases of DCIS with microinvasion
    • Patients with DCIS alone had a better 10-year distant metastasis-free survival rate than patients with DCIS with microinvasion:
      • 98% and 91%, respectively
    • The overall survival rate was also better in patients with DCIS alone:
      • 96.5% vs. 88.4%
    • However, the metastasis-free and overall survival rates were worse:
      • In patients with invasive ductal carcinoma compared with those with DCIS with microinvasion
  • In a retrospective review of the SEER database from Champion et al., 134,569 women with DCIS alone, DCIS with microinvasion, and T1a intraductal carcinoma were compared:
    • They found that the disease-specific survival of DCIS with microinvasion was significantly different from the other two groups (DCIS alone: hazard ratio [HR] 0.59, confidence interval [CI] 0.43–0.80; invasive: HR 1.43, CI 1.04–1.96) but the overall survival of DCIS with microinvasion was similar to early invasive disease
    • Patients with DCIS alone had an improved overall survival compared to DCIS with microinvasion (HR 0.83, CI 0.75–0.93)
    • These results suggest that DCIS with microinvasion should be characterized as an early invasive tumor with a good outcome and that the therapeutic approach for these patients should be similar to that for patients with invasive cancer
  • However, some studies have pointed toward DCIS with microinvasion as having a more similar natural history to DCIS alone than to early-stage invasive disease:
    • In a review of 393 patients treated at Yale between 1973 and 2004, there was no significant difference between patients with DCIS alone and those with DCIS with microinvasion with regard to the presence of axillary metastases (in those who had axillary staging) or the likelihood of recurrence (locoregional and distant) or overall survival
  • In a more recent study from Zheng et al., 308 cases of DCIS alone were compared to 92 cases of DCIS with microinvasion and 111 cases of T1a tumors:
    • With a 25-month median follow-up, their analysis demonstrated no difference in disease-free survival and overall survival among the three groups