CANCER Oncology CASE 14 February 2018 T: +27(0)51 401 9111 | - - PowerPoint PPT Presentation

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CANCER Oncology CASE 14 February 2018 T: +27(0)51 401 9111 | - - PowerPoint PPT Presentation

Dec 22, 2023 235 likes •504 views

EARLY Carika Fourie BREAST Radiation CANCER Oncology CASE 14 February 2018 T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za CASE 71 year old lady Presentation: General practitioner with a painless breast

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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

EARLY BREAST CANCER CASE

  • Carika Fourie
  • Radiation

Oncology

14 February 2018

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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

CASE

  • 71 year old lady
  • Presentation: General practitioner with a painless breast lump in left breast

for 3 months.

  • Referred to Pelonomi Hospital for work up.
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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

HISTORY:

  • Comorbidities: Hypertention on treatment for 10 years
  • Hydrochlorothiazide 25mg daily and Enalapril 5mg daily
  • Gyneacology: 3 children. No miscarriages. Never used hormonal
  • contraception. Postmenopausal for 19 years.
  • Previous knee replacement in 2011.
  • Allergic to penicillin.
  • Social: smoker, 30 pack years
  • Family history: Parents: Hypertention. Father died of myocardial infarction at
  • 57. Mother died of old age. Aunt: breast cancer at age 75.
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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

CLINICAL EXAM:

  • ECOG PS 1
  • General: No lymphadenopathy, pallor or jaundice
  • Breast: L breast: 2 cm nodule in superolateral quadrant. No skin
  • involvement. R breast: no masses
  • Chest: Good bilateral air entry. No added sounds
  • CVS: No tachycardia. S1S2 heart sounds normal.
  • Abdomen: Soft. No organomegaly.
  • Neuro: GCS 15/15. No localizing signs. Normal power in all limbs.
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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

HISTOLOGY: BIOPSY

  • Tru cut biopsy (6/9/17)
  • Grade 2 invasive ductal carcinoma
  • ER >90%
  • PR >90%
  • Her 2 negative

Subsequently had a left mastectomy and axillary dissection. Patient chose not to have breast conservation.

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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

SPECIAL INVESTIGATIONS:

  • Mammogram: Bi-RADS B breast density. Poorly circumscribed lesion in the

superolateral quadrant measuring 2 cm with increased density and pleomorphic calcifications. Ultrasound: Hypoechoic spiculated mass. Birads 4 lesion.

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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

HISTOLOGY: MASTECTOMY AND NODES

Macroscopy:

  • Skin: Normal
  • Nipple: no Paget’s
  • Single tumor nodule in superolateral quadrant
  • Tumor size: 20 x 16 x14mm
  • Surgical margins: Uninvolved, 5mm from closest surgical margin
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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

HISTOLOGY: MASTECTOMY AND NODES

Microscopy:

  • No DCIS present
  • Lymphovascular invasion
  • 0/13 lymphnodes involved
  • Ki 67 : 40%

pT1cpN0, ER/PR positive, HER2 Negative

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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

PREDICT UK:

  • Age
  • Symptomatic/not
  • Tumor size
  • Histological grading
  • Nodal status
  • ER receptor status
  • Her 2 receptor status
  • Ki 67
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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

PREDICT UK:

5 year survival:

  • 87% with no adjuvant therapy
  • 89% with hormone therapy alone
  • 89% with chemotherapy and hormone therapy

Ten year survival:

  • 68% with no adjuvant therapy
  • 71% with hormone therapy alone
  • 73% with chemotherapy and hormone therapy
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  • 1. DO WE NEED A MIND SHIFT IN OUR APPROACH TO

ADJUVANT CHEMOTHERAPY IN EARLY BREAST CANCER?

  • 2. SHOULD GENETIC PROFILING BE DONE FOR ALL EARLY

BREAST CANCER PATIENTS? WHAT ARE THE COST IMPLICATIONS? IS IT FEASIBLE, ESPECIALLY FOR STATE SECTOR?

  • 3. WHAT IS THE ROLE OF KI-67 IN GENETIC PROFILING?
  • 4. ARE WE FINALLY MOVING TOWARDS AN ERA OF

INDIVIDUALIZED TREATMENT?

  • 5. WHAT IS THE IDEAL THERAPY FOR THIS PATIENT?
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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

TREATMENT:

  • No chemotherapy
  • No radiotherapy
  • Started on Tamoxifen 20mg daily orally for 10 years
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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

IDEAL:

  • Recurrence Score(Oncotype Dx): Best validated. Place for adjuvant
  • chemotherapy. Indicated: ER positive, node negative and HER2 negative. Low

risk <18.13 (Tailorx trial: intermediate and high RS cutoffs). Node positive: Plan B study, SWOG S1007 RxPONDER trial, ongoing.

  • EndoPredict
  • Predictor Analysis of Microarray 50 (PAM50): predict susceptibility of HER2
  • verexpressed tumors to respond to HER2 directed therapy.14
  • Breast Cancer index
  • Mammaprint: 70 gene prognostic profile. Node positive tumors. MINDACT trial:

may identify a subset of patients with low likelihood of distant recurrence despite high risk features. 14

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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

Thank You

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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

ADJUVANT THERAPY

  • Reduction in mortality
  • Overtreated
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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

GENETICS

  • Prognostic and predictive markers
  • Risk profile
  • Determine benefit of adjuvant treatment
  • Prevent overtreatment of patients
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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

PROGNOSTIC FACTORS:

Clinical:

  • Age: <35 worse 5 year survival.2 Elderly patients with hormone receptor

positive breast cancer have a higher disease specific mortality3

  • Race: black women have a lower incidence of breast cancer than white

women but a higher mortality4

  • Sigarette smoke: Increased mortality in smokers5

Mammographic:

  • Screen detected breast cancer has improved overall survival compared to

clinically detected.6

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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

Pathological features:

  • Tumor size: Increased size correlates with worse prognosis and

inflammatory breast cancer even worse.7

  • Nodal involvement: Even in patients with small tumors the prognosis is

worse with nodal spread.8

  • Metastatic disease
  • Tumor morphology: ILC has a lower risk of recurrence than IDC9
  • Histological grade: Elston-Ellis grading system. Higher grade is associated

with worse prognosis.10

  • Peritumoral lymphovascular invasion: Unclear
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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

Tissue Markers:

  • Hormone receptors: Estrogen and progesterone receptors expression are

ass with improved outcomes.

  • HER2 overexpression: Worse prognosis
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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

GENOMIC PROFILES

  • Gene expression profiling: measures expression of thousands of genes in a breast cancer

cell.

  • Identified subtypes with different prognoses.
  • Luminal subtypes: ass with luminal epithelial cells of normal breast tissue
  • Luminal A: (40%). High expression of ER related genes. Low Her2 gene expression and

low expression of proliferative genes. 11

  • Luminal B: (20%). Lower expression of ER related genes. Variable expression of Her2

gene clusters and high expression of proliferation genes. Worse prognosis than Luminal A.12

  • HER2 enriched: (10-15%). High expression Her2 cluster genes as well as proliferation

gene clusters and low expression of luminal and basal clusters. Mostly ER and PR

  • negative. And HER2 overexpressed.
  • ER negative subtypes: Basal-like, claudin-low and interferon rich among others. Basal

type(15-20%). Typically triple negative

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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

PROLIFERATIVE MARKERS:

  • Ki67: Higher relapse risk and worse overall survival.16 Heterogeneity and

inconsistence of methodology of laboratories.17 ASCO does not recommend its use in assessment of prognosis.

  • Urokinase plasminogen activator system: needs validation
  • P53: due to false detection rate, not recommended.
  • Disseminated tumor cells: Assistance in determining role of adjuvant

chemotherapy not established.18

  • Circulating tumor cells: Associated with poor prognosis19 However, role in

clinical care and monitoring is uncertain and not evaluated routinely.

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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

BIOMARKER ASSAYS

  • Recurrence Score(Oncotype Dx): Best validated. Place for adjuvant
  • chemotherapy. Indicated: ER positive, node negative and HER2 negative. Low

risk <18.13 (Tailorx trial: intermediate and high RS cutoffs). Node positive: Plan B study, SWOG S1007 RxPONDER trial, ongoing.

  • EndoPredict
  • Predictor Analysis of Microarray 50 (PAM50): predict susceptibility of HER2
  • verexpressed tumors to respond to HER2 directed therapy.14
  • Breast Cancer index
  • Mammaprint: 70 gene prognostic profile. Node positive tumors. MINDACT trial:

may identify a subset of patients with low likelyhood of distant recurrence despite high risk features. 14

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T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za

CONCLUSION

  • Prognostic and predictive factors are utilized to assist in treatment

decisions.

  • Currently genomic testing assist in early breast cancer treatment.
  • Genomic testing is not readily available yet.
  • Potential markers need to demonstrate: Analytical validity, clinical validity

and clinical utility.

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REFERENCES

  • 1. NIH consensus conference. Treatment of early-stage breast cancer.

JAMA.1991;265(3):391.

  • 2. Fredholm H et al. Breast cancer in young women: poor survival despite

intensive therapy. Plos One. 2009;4(11):e7695. Epub 2009 Nov 1

  • 3. Van de Water W et al. Association between age at diagnosis and disease-

specific mortality among postmenopausal women with hormone receptor- positive breast cancer.JAMA. 2012 Feb;307(6):590-7.

  • 4. Siegel RL et al. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7.

Epub 2018 Jan 4

  • 5. Passarelli MN et al. Cigarette smoking before and after breast cancer

diagnosis:Mortality from breast cancer and smoking-related diseases. J Clin

  • Oncol. 2016;34(12):1315. Epub 2016 Jan 25
  • 6. Shen Y et al. Role of detction method in predicting breast cancer survival:

analysis of randomized screening trial. J Natl Cancer Inst. 2005 Aug;97(16): 1195-203.

  • 7. Carter CL et al. Relation of tumor size, lymph node status, and survival in

24,740 breast cancer cases. Cancer. 1989;63(1):181.

  • 8. Andersson Y et al. Breast cancer survival in relation to the metastatic tumor

burden in axillary lymph nodes. J Clin Oncol.2010 Jun;28(17):2868-73. Epub 2010 May 10

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9. Pestalozzi BC et al. Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 international Breast Cancer Study Group clinical trial. J Clin Oncol. 2008;26(18):3006. Epub 2008 May 5.10

  • 10. Singletary SE et al. Revision of the American Joint Committee on Cancer

staging system for breast cancer. J Clin Oncol. 2002;20(17):3628.

  • 11. Sotiriou C et al. Breast cancer classification and prognosis based on gene

expression profiles from a population-based study. Proc Natl Acad Sci U S

  • A. 2003;100(18):10393. Epub 2003 Aug 13.
  • 12. Voduc KD et al. Breast cancer subtypes and the risk of local and regional
  • relapse. J Clin Oncol. 2010;28(10):1684. Epub 2010 Mar 1.
  • 13. Sparano JA et al. Prostective Calidation of a 21 Gene Expression Assay in

Breast Cancer. N Engl J Med. 2015;373(21):2005. Epub 2015 Sep 27.

  • 14. Perez EA et al. Intrinsic subtype and Therapeutic Response Among HER2-

Positive Breast Tumors from the NCCTG (Alliance) N9831 Trial. J Natl Cancer Inst. 2017;109(2):1.

  • 15. Cardoso F et al. 70-Gene Signature as an Aid to Treatment Decisions in

early Breast cancer. N Engl J Med. 2016;375(8):717

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  • 16. De Azambuja E et al. Ki-67 as prognostic marker in early

breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer. 2007;96(10):1504. Epub 2007 Apr 24.

  • 17. Polley MY et al. An international Ki67 reproducibility study.

J Natl Cancer Inst. 2013;105(24):1897. Epub 2013 Nov 7.

  • 18. Harris L et al. American society of Clinical Oncology 2007

update of recommentdations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25(33):5287. Epub 2007 Oct 22.

  • 19. Lucci A et al. Circulating tumour cells in non-metastaric

breast cancer: a prospective study. Lancet Oncol. 2012 Jul;13(7):688-95. Epub 2012 Jun 6.