Introduction: Prognostic and Predictive Factors

Introduction: Prognostic and Predictive Factors
For patients without distant metastases, regional lymph node involvement image is the most important prognostic factor. The likelihood of survival diminishes with each additional positive node.
The size of invasive carcinoma image is the next most important prognostic factor. The size used for staging should incorporate clinical, radiologic, gross, and microscopic information.
TERMINOLOGY
Definitions
  • Prognostic factors
    • Predict patient clinical course in terms of risk of disease recurrence and death
    • Provide information about patient outcome based on
      • Patient-related factors: Age, menopausal status, performance status, comorbidities
      • Tumor-related factors: Lymph node staging, tumor size, grade, histologic type, lymph-vascular invasion
    • Extensively clinically validated as useful in determining probability of local &/or distant disease recurrence
      • Basis for clinical risk assessment and decisions on the need for adjuvant systemic therapy
      • Prognostic factors are robust in terms of their ability to predict disease recurrence
      • Prognostic factors are less accurate/successful at predicting patient response to systemic adjuvant therapy
    • Prognostic factors are important whether evaluated prior to therapy or after neoadjuvant therapy
      • After treatment, response to treatment and amount of residual disease are important prognostic factors
      • AJCC staging both before and after treatment provide significant prognostic information, especially in combination
    • Prognostic factors are clinically most useful in helping to identify a subset of patients with small (< 2 cm), node-negative cancer who may benefit from systemic therapy
  • Predictive factors
    • Predict the likelihood that patient will benefit from adjuvant treatment regimens including
      • Hormonal therapy
      • Chemotherapy
      • Biologic and targeted therapies
    • Provide information on the likely outcome following a specific treatment regimen
    • Development of new treatment regimens and novel targeted agents has led to a shift from risk assessment to treatment responsiveness
      • Better patient selection for specific treatments
      • Improved patient response rate
      • Reduction of toxicity from therapies that will be unlikely to be of benefit
    • Some factors, including ER, PR, and HER2, are both prognostic factors and predictive factors
CLINICAL IMPLICATIONS
Major Pathologic Prognostic Factors
  • Used for AJCC/UICC TNM staging (7th edition, 2010)
    • Used to combine patients into groups with similar likelihood of survival
    • Majority of factors are determined by readily available standard techniques
    • Useful to compare patients over time and in diverse locations
      • Essential for grouping patients for clinical trials and other studies
    • Include local extent of cancer in the breast, regional lymph node metastasis, and distant metastasis
    • Staging is prognostically important for carcinomas prior to treatment and after neoadjuvant treatment
  • Patients are divided into 5 stages with different survival rates at 10 years
    • Stage 0: DCIS; > 95% survival
      • Without screening, this group is very small (< 5% of breast cancers)
      • In screened populations, 20-30% of carcinomas are DCIS
    • Stage I: Invasive carcinomas < 2 cm with negative nodes or only micrometastases; > 90% survival
      • Approximately 50% of patients with invasive carcinoma
      • Incidence has increased with screening
    • Stage II: Invasive carcinoma up to 5 cm with 1-3 lymph node metastases or carcinoma > 5 cm with negative nodes; ˜ 60% survival
      • Approximately 30% of patients with invasive carcinoma
      • Incidence has decreased with screening
    • Stage III: Locally advanced disease (skin ulceration or chest wall invasion or inflammatory carcinoma) ± lymph node metastases or metastases in ≥ 10 lymph nodes; ˜ 40% survival
      • Only 5-10% of patients
      • Incidence has decreased due to greater awareness and earlier detection
    • Stage IV: Distant metastases; < 10% survival
      • Only 5-10% of patients
      • Incidence has not changed substantially over time
      • Likely a subset of carcinomas that metastasize early prior to possible detection by screening
  • Size of invasive carcinoma (AJCC T1-3)
    • Size of an invasive carcinoma is an independent prognostic factor
      • Does not include associated carcinoma in situ
      • Correlated with likelihood of lymph node metastasis
      • Clinical, radiologic, gross, and microscopic information should be used to determine best size for T classification
      • Palpable carcinomas have worse prognosis compared with nonpalpable carcinomas, detected by screening, of same size
    • Tumor size directly correlates with number of involved lymph nodes and an increased risk of recurrence
      • For node-negative patients, tumor size is routinely used to make adjuvant treatment decisions
      • Patients with carcinomas ≤ 1 cm have an excellent prognosis, and selected patients have little benefit from systemic therapy
    • AJCC T classification separates majority of carcinomas by size
    • T1 carcinomas are ≤ 2 cm in size
      • T1mi: ≤ 0.1 cm (microinvasion)
      • T1a: > 0.1 cm but ≤ 0.5 cm
      • T1b: > 0.5 cm but ≤ 1 cm
      • T1c: > 1 cm but ≤ 2 cm
    • T2: > 2 cm but ≤ 5 cm
    • T3: > 5 cm
    • T4: Tumor of any size with direct extension to chest wall or skin involvement or inflammatory carcinoma
  • Regional lymph nodes (AJCC N1-3)
    • Prognosis diminishes with each additional lymph node metastasis
      • N0: Negative nodes, 82.8% 5-year survival
      • N1a: 1-3 positive nodes, 73% 5-year survival
      • N2a: 4-9 positive nodes, 45.7% 5-year survival
      • N3a: 10 or more positive nodes, 28.4% 5-year survival
    • Prognosis is dependent on size of the metastasis
      • Macrometastases measure > 2 mm and have prognostic significance
      • Isolated tumor cells (< 0.2 cm or < 200 cells) & micrometastases (between isolated tumor cells & macrometastases) have very small effect on prognosis compared to node-negative women
      • Total number of positive nodes includes macrometastases and micrometastases but not isolated tumor cells
      • Patients with only micrometastases are classified as stage I in AJCC 7th edition manual
    • Subset (10-30%) of node-negative patients eventually develop distant metastases
      • Some of these carcinomas may metastasize to nodal basins that are generally not sampled (e.g., internal mammary nodes)
      • Other carcinomas may metastasize primarily via blood vessels (e.g., spindle cell carcinomas)
    • Lymph nodes are removed or sampled primarily for prognostication
      • Removal of positive lymph nodes has little or no effect on survival
  • Distant metastases (AJCC M1)
    • Generally detected clinically or radiologically
      • Patients with indeterminant findings may undergo biopsy for confirmation
      • M1 metastases are detected by clinical or radiologic means &/or are pathologically shown to be > 0.2 mm
      • M0 (i+) metastases are detected by microscopy or other tests and are ≤ 0.2 mm; are not evident clinically or radiologically or by symptoms or signs
    • Patients with M1 (stage IV) disease have a poor prognosis, < 10% survival at 10 years
      • Patients who present with distant metastases at a long interval after diagnosis have a better prognosis
      • Indicative of a carcinoma with a slower growth rate
    • Most common sites of metastasis are bone, lung, brain, and liver
      • Bone is most common site and, in ER-positive cancers, may occur many years after diagnosis
      • Brain metastases are relatively more common in HER2-positive cancers and triple negative cancers
    • Pathologic M0 can only be defined at autopsy
      • For living patients, only clinical M0 is applicable
    • MX was eliminated as a term in the AJCC 7th edition
  • Skin involvement, chest wall involvement, or inflammatory carcinoma (AJCC T4)
    • Extensive skin &/or chest wall involvement originally identified in patients with very large locally advanced carcinomas who would not benefit from surgery
      • Current prognosis is improved with better surgical and adjuvant treatment
      • Difficult to study as these patients are now quite uncommon
    • T4a: Extension to chest wall
      • Does not include adherence to or invasion of pectoralis muscle
    • T4b: Skin involvement
      • Ulceration of skin: Does not include ulceration due to a prior surgical procedure or Paget disease of the nipple
      • Small superficial carcinomas with ulceration are unlikely to have the poor prognosis associated with large ulcerating carcinomas (but do have increased likelihood of lymph node metastases)
      • Satellite skin nodules: Invasive carcinoma in skin not contiguous with the main carcinoma; generally due to extensive lymph-vascular invasion
      • Edema (including peau d’orange) is not sufficient for diagnosis of inflammatory carcinoma; this finding cannot be determined in surgical excisions and is rarely used for staging
    • T4c: Features of both T4a and T4b
    • T4d: Inflammatory carcinoma
      • Defined by clinical sign of diffuse erythema and edema (peau d’orange) involving 1/3 or more of skin of the breast
      • Correlates with a type of carcinoma characterized by extensive dermal lymph-vascular invasion
      • Pathologic finding of dermal lymph-vascular invasion has a poor prognosis, but in absence of clinical signs is insufficient for classification as inflammatory carcinoma
Additional Pathologic Prognostic Factors
  • Important for prognosis but not currently incorporated into AJCC staging
  • Histologic grade
    • Used to stratify breast cancer patients into favorable (well-differentiated) and less favorable (poorly differentiated) outcome groups
    • A number of different breast cancer grading systems have been clinically validated
    • Nottingham combined histologic grade (Elston-Ellis modification of Scarff-Bloom-Richardson grading system) is recommended by the College of American Pathologists, the American Joint Commission on Cancer, and the European Working Group on Breast Screening Pathology
      • Grade is based on evaluation of glandular (acinar)/tubular differentiation, nuclear score, and mitotic score
      • Adherence to strict morphologic criteria is needed for reproducibility so that grade is reliably useful as a prognostic factor
    • Grade 2 cancers may be a mixture of grade 1 and 3 cancers
      • Proliferative rate may be used to reclassify grade 2 cancers
    • Extensive necrosis (> 1 high-power field) identifies grade 3 cancers with a particularly poor prognosis
      • Necrosis is predictive of a good response to chemotherapy
  • Lymph-vascular invasion (LVI)
    • Peritumoral LVI has prognostic significance for risk of local and distant recurrence
      • Recurrence for stage I disease with LVI is ˜ 38% compared with 22% in its absence
    • Closely associated with lymph node metastases but is an independent factor
      • Prognosis is diminished if both LVI and nodal metastases are present
    • Currently unnecessary to distinguish small capillaries from lymphatics using IHC markers
      • Both have prognostic significance
  • Special histologic types of invasive carcinoma
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Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Introduction: Prognostic and Predictive Factors

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