Pharmacotherapy of Breast Cancer

PST 06106

Basic Pharmacotherapy

Session 31: Pharmacotherapy of Breast

Cancer

Learning Objectives

By the end of this session students are expected to be able to:

Define breast cancer

Explain pathophysiology of breast cancer

Explain the clinical presentation of breast cancer

Outline diagnosis of breast cancer

Describe pharmacological treatment of breast cancer

Describe the monitoring of breast cancer

therapy

Definition of Breast Cancer

Breast cancer is a malignancy originating from breast tissue.

Disease confined to a localized breast lesion is referred to as early, primary, localized, or curable

Disease detected clinically or radiologically in sites distant from the breast is referred to as advanced or metastatic breast cancer (MBC), which is usually incurable.

Breast cancer cells often spread undetected by

contiguity(bordering/being in contact with something),

lymph channels, and through the blood early in the course of the disease, resulting in metastatic disease after local therapy.

The most common metastatic sites are lymph nodes, skin, bone, liver, lungs, and brain

.

Activity: Buzzing

What is the pathophysiology of breast cancer?

Pathophysiology of Breast Cancer

Breast cancer is a malignant tumor that starts in the cells of the

breast

,

Like

other cancers, there are several factors that can raise the risk of getting breast cancer:

Female gender

Age

Previous breast cancer

Benign breast disease

Hereditary factors (family history of breast cancer)

Pathophysiology of Breast

Cancer

Cont

…

Early age at menarche

Late age at menopause

Late age at first full-term pregnancy

Obesity (postmenopausal)

Low physical activity

High-dose exposure to ionizing radiation early in life

Pathophysiology of Breast Cancer

Cont.…

Damage to the DNA and genetic mutations can lead to breast cancer; have been experimentally linked to estrogen exposure.

Some

individuals inherit defects in the DNA and genes like the BRCA1, BRCA2 and P53 among others.

Those

with a family history of ovarian or breast cancer thus are at an increased risk of breast cancer

.

BRCA1

and

BRCA2

are human genes that produce tumor suppressor proteins.

These

proteins help repair damaged DNA and, therefore, play a role in ensuring the stability of each cell’s genetic material.

When

either of these genes is mutated, or altered, such that its protein product is not made or does not function correctly, DNA damage may not be repaired properly

..

Pathophysiology of Breast Cancer

Cont

…

The immune system normally seeks out cancer cells and cells with damaged DNA and destroys them.

Breast

cancer may be a result of failure of such an effective immune defense and surveillance.

These are several signalling systems of growth factors and other mediators that interact between stromal cells and epithelial cells. Disrupting these may lead to breast cancer as well.

Clinical Presentation and Diagnosis of Breast Cancer

The patient may not have any symptoms, as breast cancer may be detected in asymptomatic patients though routine screening mammography.

The initial sign in more than 90% of women with breast cancer is a painless lump that is typically solitary, unilateral, solid, hard, irregular, and

non mobile

.

Less common initial signs are pain and nipple changes.

More advanced cases present with prominent skin

oedema,

redness, warmth, and induration.

Symptoms of MBC depend on the site of metastases, but may include bone pain, difficulty breathing, abdominal pain or enlargement, jaundice, and mental status changes.

Many women first detect some breast abnormalities themselves, but it is increasingly common for breast cancer to be detected during routine screening mammography in asymptomatic women

.

Clinical Presentation and Diagnosis of Breast

Cancer Cont.….

Staging

Stage

is based on the size of the primary tumor, presence and extent of lymph node involvement, and presence or absence of distant metastases. Simplistically stated, these stages may be represented as

follows:

Early Breast Cancer

Stage 0: Carcinoma in situ or disease that has not invaded the basement

membrane.(is

a group of abnormal cells that are found only in the place where they first formed in the body

)

Stage I: Small primary

tumour

without lymph node involvement.

Stage II: Involvement of regional lymph nodes.

Clinical Presentation and Diagnosis of Breast Cancer Cont.….

Locally Advanced Breast Cancer

Stage III: Usually a large tumor with extensive nodal involvement in which node or tumor is fixed to the chest wall; also includes inflammatory breast cancer, which is rapidly progressive.

Advanced or Metastatic Breast Cancer

Stage IV: Metastases in organs distant from the primary

tumour.

Clinical Presentation and Diagnosis of Breast Cancer Cont.….

Clinical Presentation

Local

Signs and Symptoms

A painless, palpable lump is most common.

Less common: pain; nipple discharge, retraction or dimpling;

Skin edema, redness or warmth.

Palpable local–regional lymph nodes may also be

present

Signs and Symptoms of Systemic Metastases

Depends on the site of metastases, but may include bone pain, difficulty breathing, abdominal pain or enlargement, jaundice, mental status

changes

Clinical Presentation and Diagnosis of Breast Cancer Cont.….

Diagnosis

Initial workup for a woman presenting with a localized lesion or suggestive symptoms should include a careful history, physical examination of the breast, three-dimensional mammography, and, possibly, other breast imaging techniques such as ultrasound.

Breast biopsy is indicated for a mammographic abnormality that suggests malignancy or a mass that is palpable on physical examination.

Clinical Presentation and Diagnosis of Breast Cancer Cont.….

Laboratory Tests

Tumor markers such as cancer antigen (CA) or carcinoembryonic antigen (CEA) may be elevated.

Alkaline phosphatase or liver function tests may be elevated in metastatic disease.

Clinical Presentation and Diagnosis of Breast Cancer Cont.….

Other Diagnostic Tests

Mammogram

(with or without ultrasound, breast MRI, or both)

Biopsy for pathology review and determination of tumor estrogen/progesterone receptor (ER/PR) status and

HER2

status.

Systemic staging tests may include: chest x-ray, chest CT, bone scan, abdominal CT or ultrasound, or MRI

.

Activity

: Small Group Discussion

What

is the pharmacological treatment of breast cancer?

Pharmacological Treatment of Breast Cancer

Chemotherapy is indicated for almost all patients as neo-adjuvant, adjuvant or palliative. Patients, who are planned for surgery and have ≥ T3 tumors, should receive neo-adjuvant chemotherapy before

operation

Several

regimens are available. Few of them include

:

Dosing schedules for combinations for HER 2 negative disease:

Pharmacological Treatment of Breast

Cancer

Cont

…

Describes cancer cells that do not have a large amount of a protein called HER2 on their surface. In normal cells, HER2 helps to control cell growth. Cancer cells that are HER2 negative may grow more slowly and are less likely to recur (come back) or spread to other parts of the body than cancer cells that have a large amount of HER2 on their surface

Pharmacological Treatment of Breast Cancer

Cont

…

weeks.

Doxorubicin

60 mg/m2 IV on day1 + Cyclophosphamide 600 mg/m2 IV day 1 given every 21 days for 4 cycles then followed by Paclitaxel 175 mg/m2 by 3 h IV infusion day 1, given every 21 days for 4 cycles OR Docetaxel 100 mg/m2 IV day 1 Cycled every 21 days for 4 cycles.

NOTE:

FBC(Full blood count), RFT(Renal function test), LFT( Liver function test)

before each cycle

Pharmacological Treatment of Breast Cancer

Cont

…

Dosing schedule for combinations for HER2-Positive disease:

wks

AND

Pharmacological Treatment of Breast Cancer

Cont

…

Endocrine

therapy

Monitoring

of Breast Cancer Therapy

Monitoring response to treatment is a key element in the management of breast cancer that involves several different viewpoints from surgery, radiology, and medical oncology

After completion of adjuvant therapy, follow up care focuses on detecting recurrent disease with the intention of improving long term survival

Monitor patient adherence to the treatment as maintaining dose intensity has been demonstrated to be important in the cure of disease

Tumor response to a particular treatment regimen may be measured by clinical chemistry such as liver enzyme elevation in a patient with hepatic metastases or tumor markers, or imaging techniques such as bone scans or chest radiographs.

Monitoring

of Breast Cancer

Therapy

Cont

…

However, assessment of the patient’s clinical status and symptom control is often adequate to evaluate response to the therapy administered.

In the patient with metastatic breast cancer, it is common to initiate hormonal therapy or chemotherapy and continue administration until signs and symptoms of disease progression or new signs and symptoms present

Monitor the adverse effects of drugs and manage them accordingly

Key Points

Breast

cancer is a malignancy originating from breast tissue. Disease confined to a localized breast lesion is referred to as early, primary, localized, or curable

Disease detected clinically or radiologically in sites distant from the breast is referred to as advanced or metastatic breast cancer (MBC), which is usually incurable

Key

Points Cont.….

Damage to the DNA and genetic mutations can lead to breast cancer; have been experimentally linked to estrogen exposure. Some individuals inherit defects in the DNA and genes like the BRCA1, BRCA2 and P53 among others. Those with a family history of ovarian or breast cancer thus are at an increased risk of breast cancer.

Chemotherapy is indicated for almost all patients as neo-adjuvant, adjuvant or palliative. Patients, who are planned for surgery and have ≥ T3 tumors, should receive neo-adjuvant chemotherapy before operation

Evaluation

What

is Breast Cancer?

What is the pathophysiology of Breast Cancer?

How is Breast Cancer diagnosed?

How is monitoring of Breast Cancer therapy done?

References

Wells

BG,

DiPiro

J,

Schwinghammer

T (2013),

Pharmacotherapy Handbook

(6

th

Ed). New York, NY: McGraw-Hill.

DiPiro

JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008):

Pharmacotherapy: A Pathophysiologic Approach

(7

th

ed

): New York, NY: McGraw-Hill.

Katz M D.,

Matthias KR.,

Chisholm-Burns M A.,

Pharmacotherapy (2011)

Principles & Practice Study Guide: A Case-Based Care Plan Approach

:

New York, NY: McGraw-Hill.

Schwinghammer

TL, Koehler JM (2009)

Pharmacotherapy Casebook: A Patient-Focused Approach

(7

th

ed

): New York, NY: McGraw-Hill.

Unataka kutumiwa notes hizi kupitia WhatsApp?Kwa notes zilizopangiliwa vizuri kwa kusoma offline au PDF, bonyeza kitufe hapa chini. Ujumbe wenye Level, Semester, Module na Topic utaandaliwa moja kwa moja.TUMIWA NOTES WHATSAPP