Multi Disciplinary Cancer Multi Disciplinary Cancer Management –Breast Management –Breast CancerCancerDr Masalu N. MDMedical Oncologist

Breast Cancer Statistics IIMedical Oncologist

•Nearly 50% of diagnoses and 60% of breast cancer deaths occur in underdeveloped countries•Breast cancer 5 year survival ~89% in US (survival 75.2% in 1975), less than 40% in low income countries •Screening reduces deaths from breast cancer in developed countries; impact of screening unknown in low income countries

CA Cancer J Clin 2011, NCI SEER 2012, Lancet Oncology 2008

StageStage 5 year survival5 year survival0 100%I 100%II 93%III 72%IV 22%

Most breast cancer cases in Tanzania present with stage IIIB or IV disease

*NCI seercancer.gov

Breast Cancer Survival According to Stage at

DiagnosisMedical Oncologist

Over 90% of US breast cancer cases present with localized or regional disease (nodes)*

Ductal Carcinoma In-Situ (DCIS) of the Breast

Pathologist• Clinical presentation: Incidental finding,

mass, abnormal mammogram• Natural history: Limited studies but up to

30% of women with partially resected lesions develop invasive cancer at 6-10 years

• Treatment: Mastectomy (99% cure) vs. lumpectomy +/- XRT

• Consider endocrine therapy for five years, especially if tumor ER positive

Lobular Carcinoma In-SituPathologist

• Clinical presentation: May lack mammographic signs, incidental, more common in premenopausal women, often multifocal or bilateral

• Natural history: Not a cancer but marker for increased risk (subsequent carcinoma in opposite breast 50% of the time and more often ductal histology)

• Risk of invasive cancer: ~1% annually• Treatment: Cautious observation, rarely

prophylactic bilateral mastectomy

Community

VolunteersSpiritual counselor Nurse

Hospice workerPhysical therapist

Pharmacist

Physician Psychologist

SocialWorker

Family

Patient

Interdisciplinary TeamInterdisciplinary TeamMedical OncologistMedical Oncologist

Normal cells know :

• When to grow• How to differentiate • When to stop growing • When to die (apoptosis)

Neoplastic cells:

• Grow too much• Do not differentiate• Do not stop growing• Do not die

Malignant cancer cells can metastasize (spread

Pathologic features important in Pathologic features important in determining breast cancer determining breast cancer

treatmenttreatmentEstrogen and Progesterone receptors are located in

the nucleus of the cell and are important factors in cell growth

Estrogen and progesterone receptor status, HER-2/neu, +/- Ki-67 status have documented clinical usefulness as tumor markers and choice of therapy

Molecular profile (costly; limited access)

Breast Cancer SubtypesBreast Cancer SubtypesPathologistPathologist

Subtype Pathology Prevalence

Characteristics

Luminal A ER and/or PR +HER2-Low Ki67Grade 1-2

30-70% -Best prognosis-Fairly high survival rates-Fairly low recurrence rates

Luminal B -ER and/or PR +-HER2+ or HER2- and high Ki67-Higher tumor grade -Larger tumor size-More often node+

10-20% -Prognosis good, but-Survival not as high as luminal

Triple negative (basal-like)

ER and PR-HER2-

15-20% -Aggressive -Poorer prognosis in first 5 years

HER2 Type ER and PR-Typically HER2+

5-15% -Younger age-Outcome improved with introduction of anti-HER2 agents

Treatment of cancer is multidisciplinaryTreatment of cancer is multidisciplinary Medical Oncologist Medical OncologistSurgery Tumor removalRadiation DNA DamageChemotherapy DNA Disruption or damageTargeted Therapy Selective signal blockingGene Therapy Replacement of gene function

FUTURE: Personalized therapy“Identify which therapy will be more successful for each

patient”

Primary Consultation: MS• MS is 52 years old• She works as a manager• She has had a mass in her left breast for one

year

• No pain• No nipple secretion• No skin changes or

swollen glands

Pregnancies 4Deliveries 3Menarche at age 12; last period at 50Never had a breast biopsy

• Mother breast cancer at age 62 and a second primary at age 68

• Sister breast cancer at age 57• Maternal aunt breast cancer at age 59

• Maternal aunt ovarian cancer at age 68• Maternal uncle colon cancer at age 65• HBOC,BRCA1,BRCA2,LYNCH SYNDROME-

HNPCC

Family HistoryFamily History

• Vital signs: Temp 36.2 Pulse 89 Blood Pressure 137/67

• A large 6x8 cm movable breast mass, without skin changes

• Axilla: Several enlarged lymph nodes

• Supraclavicular and cervical nodes: negative

• Liver feels normal

Should we order a Should we order a mammogram?- Radiologistmammogram?- RadiologistA. No needB. Only for the affected breastC. Only for the normal breastD. Mammogram for both breasts prior to

biopsyE. Not now, only after treatment

Craneo-CaudalMedio-LateralCraniocaudalMediolateral

Patient mammogram BIRAD 5Patient mammogram BIRAD 5

What should the primary What should the primary physician do? -Radiologistphysician do? -RadiologistA. Refer to surgeon for biopsyB. Refer for chest x-ray and bone scanC. Give antibioticsD. Removal of breast without biopsyE. Send home with pain medicines

Surgeon’s checklistSurgeon’s checklist

Need to order mammogram if not already done Need to confirm diagnosis with tissue biopsyRemember to order receptors estrogen,

progesterone, Her2-neu and Ki-67Consider staging tests for locally advanced

disease

What kind of biopsy would you What kind of biopsy would you do? Surgeondo? SurgeonA. Core-needle biopsyB. Fine-needle aspirationC. Excisional biopsyD. Punch biopsyE. None of the above

Tissue –Sent to Pathologist

Information given:

-Breast “lump”-Do receptors (estrogen, progesterone, Her2-neu, Ki-67)

Is this enough information for the pathologist?

Normal breast (skin, fat, breast tissue)

Hyperplasia with calcifications: Hematoxylin & Eosin

Ductal infiltrating carcinoma

Estrogen Receptor

Progesterone Receptor

Pathology Report:

-Infiltrating Ductal Carcinoma Grade III some areas of in situ cancer

-Estrogen and progesterone receptors negative, HER2-neu not amplified, Ki-67 25%

Breast Cancer SubtypesBreast Cancer SubtypesSubtype Pathology Prevalen

ceCharacteristics

Luminal A ER and/or PR +HER2-Low Ki67Grade 1-2

30-70% -Best prognosis-Fairly high survival rates-Fairly low recurrence rates

Luminal B -ER and/or PR +-HER2+ or HER2- and high Ki67-Higher tumor grade -Larger tumor size-More often node+

10-20% -Prognosis good, but-Survival not as high as luminal

Triple negative (basal-like)

ER and PR-HER2-

15-20% -Aggressive -Poorer prognosis in first 5 years

HER2 Type ER and PR-Typically HER2+

5-15% -Younger age-Outcome improved with introduction of anti-HER2 agents

What investigations would you What investigations would you do to complete the staging?-do to complete the staging?-RadiologistRadiologist

Laboratories?CXRChest CT?Abdominal ultrasound?Abdominal CT scan?CT scan brain?Bone scan?PET scan?

Please discuss

Patient Summary-RadiologyPatient Summary-RadiologyMammogram right breast normal

6x8cm mass left breast – highly suspicious for malignancy BIRAD 5

Pathology reports infiltrating ductal carcinoma, high grade(III)

ER and PR negative, Her2-neu not amplified (triple negative)

Staging studies negative

MS Case Summary-Medical OncologyMS Case Summary-Medical OncologyMammogram right breast normal6x8cm mass left breast – highly suspicious for

malignancy BIRAD 5Pathology reports infiltrating ductal carcinoma, high

gradeER, PR negative, Her2-neu not amplified (Triple

negative)Staging studies negativeClinical Stage: T3 N2 M0

What do you think should be done?What do you think should be done?Medical OncologistMedical OncologistA. Radical mastectomyB. Modified radical mastectomyC. Referral to medical oncology for

neoadjuvant treatmentD. Referral to radiation oncology for pre-

operative external beam radiationE. Palliative care

Discussion – case summaryDiscussion – case summaryMammogram right breast normal6x8cm mass left breast – highly suspicious for

malignancy BIRAD 5Pathology reports infiltrating ductal carcinoma, high

gradeER, PR negative, Her2-neu not amplified (Triple

negative)Staging studies negativeClinical Stage: T3 N2 M0 (Stage III)

Tumor Conference Treatment Plan:Tumor Conference Treatment Plan:Neoadjuvant treatment

Salvage mastectomy

External radiation therapy

Suppressive endocrine therapy ??

Follow up

Medical Oncologist’s thoughts, goalsMedical Oncologist’s thoughts, goals

Healthy 52 year old woman with locally advanced breast cancer, triple negative, disease still seems localized to the breast and axilla.

Neoadjuvant treatment (chemotherapy prior to surgery) will reduce tumor size and allow a mastectomy or perhaps a lumpectomy in selected cases.

In Fact post AC4 +T4 tumour size went down to 2x2 cm.

T1yNxMx.

Medical Oncologist’s thoughtsMedical Oncologist’s thoughtsMS does not qualify for post-operative

endocrine therapy (Tamoxifen or aromatase inhibitors) because as her tumor was ER/PR negative

She does not qualify for anti-HER2-neu therapy as her tumor was HER2 negative.

Survival According to Treatment: Stage IIISurvival According to Treatment: Stage III

Treatment No. of Patients

5-Year Survival

Surgery only 2,453 36%

Radiation only 2,386 29%

Surgery plus radiation 4,249 33%

Chemotherapy, Surgery, and Radiation 1,923 63%

Giordiano SH. Oncologist. 2003;8:521-530.