BREAST CANCER

Dr Wuraola Akande
PCL 404
OUTLINE
• INTRODUCTION
• CLASSIFICATION
• PATHOPHYSIOLOGY
• CLINICAL STAGING
• EPIDEMIOLOGY
• RISK FACTORS
• SIGNS AND SYMPTOMS
• DIAGNOSIS
• PREVENTION & PROGNOSIS
• TREATMENT
• ADVANCES IN TREATMENT
2
• COMPLICATIONS
• REFERENCES
INTRODUCTION
• It is an uncontrolled growth of normal cells in the breast.
• It can be described as
• ductal
• Lobular
• In-situ
• infiltrating or invasive breast cancer.
• Other forms are:
• locally advanced breast cancer
• inflammatory breast cancer
• pagets disease of the breast
• metastatic breast cancer etc 3
Anatomy of the breast

4
CLASSIFICATION
• Cancer is staged according to the tumor, nodes, metastases
(TNM) system described in stages I to IV.
• Breast cancer is classified into major molecular subtypes
according to hormone and growth factor receptor
expression:
• Luminal A (HR+/HER2-)

• HER2+

• Luminal B (HR+/HER2+)
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• Triple negative (HR-/HER2-)
PATHOPHYSIOLOGY
• Pathology of BC establishes histologic diagnosis and
confirms presence or absence of prognostic factors
including:
• necrosis, lymphatic or vascular invasion,
• nuclear grade, hormone receptor status,
• proliferative index, amount of aneuploidy, and
• HER-2/neu gene amplification or protein expression.
• BC may be Invasive or Non-invasive
• Invasive carcinoma (adenocarcinomas) are classified as
ductal or lobular
• Infiltrating lobular carcinoma commonly metastasizes to
meningeal and serosal surfaces,
• ductal carcinomas usually metastasize to the bone, brain, or 6
liver.
PATHOPHYSIOLOGY
• Noninvasive lesions may also be broadly divided into
ductal and lobular categories (mainly carcinoma in situ –
DCIS and LCIS).
• DCIS is diagnosed more frequently than LCIS.
• Simple or total mastectomy is the standard treatment for
DCIS.
• Breast conservation may be an effective alternative to
mastectomy.
• it significantly reduces the incidence of local recurrences
and enhances the breast preservation rate in women with
DCIS (Chisholm-Burns et al., 2013).
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PATHOPHYSIOLOGY
• Only 1% incidence of axillary node involvement in
DCIS, ALND is rarely indicated.
• Currently, no proven benefit for the use of cytotoxic
chemotherapy.
• DCIS in HR+ patients may require tamoxifen with
lumpectomy and radiation (Chisholm-Burns et al., 2013).

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CLINICAL STAGING
• Stage 0 - carcinoma in situ
• Stage I – small primary tumor without lymph node
involvement
• Stage II - involves regional lymph nodes
• Stage III - locally advanced disease, usually a large tumor
with extensive nodal involvement in which either node or
tumor is fixed to the chest wall.
• Stage IV - presence of metastases to organs distant from
the primary tumor. Also known as advanced or metastatic
disease (Chisholm-Burns et al., 2013).
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EPIDERMIOLOGY
• Breast cancer can occur in both men and women
• It has overtaken cervical cancer as the leading female
malignancy
• It is the most frequent cancer and greatest cause of cancer
mortality among women
• Affects over 2.1 million women annually and about 627,
000 deaths in 2018 (WHO, 2019).
• The most commonly diagnosed & second leading cause
of cancer mortality in women in the US (Siegel et al.,
2017).
• It is responsible for about 16% of all cancer related 10
deaths in Nigeria (Omogbadegun, 2013) .
RISK FACTORS
• Female • Overweight
• Age • Birth control pills
• Family history • Alcohol and smoking
• Genetics • Not having children
• Cosmetic implants
• Radiation exposure
• Dense breast
• Early onset of menstruation

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• Late menopause
SIGNS AND SYMPTOMS
• Breast pain and/or lump

• Change in size or shape of the breast

• Flaking, crusting, peeling, scaling of the areola

• Skin dimpling or skin changes (e.g. thickening,

swelling, or redness)
• Nipple inversion or skin change or nipple
abnormalities 12

• Axillary lump (Chalasani and Kiluk, 2018).

DIAGNOSIS
• Physical examination
• Mammography
• Ultrasound
• MRI
• Biopsy

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PREVENTION
• Breast examination
• Exercise
• Healthy weight
• Correct diet
• Alcohol moderation
• Postmenopausal hormone therapy limitation
• Preventive medications e.g. estrogen blocking
medications, aromatase inhibitors
• Preventive surgery e.g. mastectomy and oophorectomy
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PROGNOSIS
• Prognostic factors are biological or clinical factors
associated with breast cancer survival without
considering effect of therapy.
• Poor prognostic factors include:
• Age younger than 35 years
• Larger tumor size
• High nuclear grade signifies that a tumor is growing
quickly
• Lymph node involvement
• Negative tumor receptor status (i.e., ER-, PR-, and
HER2-) 15

• Over-expression of HER-2
TREATMENT
• Primary treatment is surgery
• Goal of surgery include:
• complete resection of the primary tumor with negative
margins
• pathologic staging of the tumor and axillary lymph nodes
(ALNs).
• Adjuvant treatment of breast cancer is designed to treat
micrometastatic disease
• Adjuvant treatment involves:
• radiation therapy and
• systemic therapy including a variety of chemotherapeutic,
hormonal and biologic agents (Chalasani and Kiluk, 2018).
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TREATMENT - Surgery
• This depends on the stage of cancer.
• Types of surgery include:
o Lumpectomy: this means removing the tumor and some
healthy cells around it.
o Mastectomy:
o Simple mastectomy involves removing nipples, duct, lobules,
areola and some skin
o radical involves removal of muscles as well as lymph nodes
(ALND).
o Sentinel node biopsy: removal of lymph nodes
o Auxiliary lymph node dissection: removal of several lymph
nodes once the sentinel node becomes cancerous.
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TREATMENT – Systemic Adjuvant
Therapy
• Includes chemotherapy, hormone therapy and use of
biologic agents
• Chemotherapy is the use of cytotoxic drugs to kill cancer
cells. May be used with or without hormonal or biologic
therapy or biologics in the following conditions:
• if there is a high risk of spread or recurrence after surgery -
ADJUVANT CHEMOTHERAPY
• If shrinkage is necessary before surgery - NEO-ADJUVANT
CHEMOTHERAPY
• If cancer has metastasized to other parts of the body
• If decrease in estrogen production is needed
• Adverse effects include: nausea, vomiting, alopecia, higher
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susceptibility to infections, anorexia, sore mouth.
Principles of Combination Chemotherapy
• The knowledge of tumor growth kinetics has been used to
optimize chemotherapy.
• The most rapid growth occurs at small tumor volumes.
• Large tumors may be less sensitive to agents that selectively
target dividing cells.
• Principles of combination therapy (adjuvant chemotherapy)
based on cell kinetics and pharmacology include:
• Drugs known to be active as single agents should be selected for
use in combination; preferably drugs that induce complete
remission should be used.
• Drugs with different MOA that have additive or synergistic
cytotoxic effects on the tumor cells should be combined
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Principles of Combination Chemotherapy
• Drugs with different dose-limiting toxicities should be combined
so that full or nearly full therapeutic doses can be utilized
• Drugs should be used at optimal dose and schedule
• Drugs should be given at constant intervals, with treatment free
period that is as short as possible
• Drugs with different patterns of resistance should be used to
minimize cross-resistance.
• Combination chemotherapy provide advantages such as:
• Maximize cell kill with minimum host cell toxicities by using
agents with non-overlapping dose-limiting toxicities
• Increase spectrum of drug activity against tumor cells with
endogenous resistance to specific types of therapy.
• Slow or prevent incidence of resistance tumor cells (Takimoto and
Calvo, 2005). 20
 Summary of treatment options for BC
subtypes
Table 1- Systemic adjuvant therapy options for operable breast cancer*
Breast cancer subtype/classification Adjuvant systemic therapy
Phenotypic Intrinsic subtype Endocrine Anti-HER-2 Chemotherapy
subtype therapy therapy
Hormone HER-2
receptor overexprexssion
+ - Luminal A or B Yes No Yes (if high risk)
+ + Luminal B or HER- Yes Yes Yes
2 enriched
- - Basal or TNBC No No Yes
- + HER-2 enriched No Yes Yes

*Anampa et al., 2015

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TREATMENT: Adjuvant Chemotherapy
• The most commonly used cytotoxic agents are:
• cyclophosphamide, methotrexate, 5-fluorouracil, doxorubicin and
epirubicin.
• The anthracycline-containing regimens are slightly superior
• Addition of taxane to an anthracycline-containing regimen
may further increase the efficacy of adjuvant chemotherapy.
• The taxanes (paclitaxel or docetaxel) plus anthracyclines are
the most active chemotherapy drugs against breast cancer.
• The best results are achieved with 2nd and 3rd-line drugs:
• capecitabine, vinorelbine, gemcitabine, 5-fluorouracil and a
variety of its oral pro-drugs (Boer, 2002)
• Dose intensity and dose density are critical factors in achieving
optimal outcomes in adjuvant breast cancer therapy (Chisholm- 22
Burns et al., 2013).
Regimens for Adjuvant Chemotherapy
Table 2 – Adjuvant chemotherapy regimens (Anampa et al., 2015)
Generation Benefit Regimen (evidence based)
First-line 35 % reduction in breast cancer mortality CMFx6, ACx4, FEC50x6
compared with no adjuvant chemotherapy
Second-line 20 % reduction in breast cancer mortality FEC100x6, CAFx6, FACx6
compared with first generation regimen ACx4-Tx4 (q3wks)
DCx4, Ex4-CMFx4
Third-line 20 % reduction in breast cancer mortality FECx4-Dx3, FECx4-weekly Tx8
compared with second generation regimen Concurrent DAC
Dose-dense ACx4-Tx4
ACx4-weekly paclitaxel
ACx4-docetaxel (q 3 weeks)

CMF, Cyclophosphamide, methotrexate, 5-flourouracil; AC, Doxorubicin, cyclophosphamide;

FEC50, 5-flourouracil, epirubicin (50 mg/m2), cyclophosphamide;
FEC100, 5-flourouracil, epirubicin (100 mg/m2), cyclophosphamide;
DC, Docetaxel, cyclophosphamide; CAF, Cyclophosphamide, doxorubicin, 5-flourouracil;
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FAC, 5-flouroracil, doxorubicin, cyclophosphamide;
DAC, Docetaxel, doxorubicin, cyclophosphamide; T, paclitaxel; D, Docetaxel; E, Epirubicin
TREATMENT - Hormone blocking therapy
• This prevents recurrence in hormone-sensitive breast cancers
called estrogen receptor (ER) positive and progesterone
receptor (PR) positive cancers.
• About 50% to 70% of patients with primary or metastatic
breast cancer have hormone receptor–positive tumors.
• Can be used alone, prior to or after surgery.
• Examples include:
• Tamoxifen 20mg PO q24hrs
• Aromatase inhibitor e.g
• Anastrozole 1 mg PO q24hr
• Letrozole 2.5 mg PO q24hr
• Exemestane 25 mg PO q24hr
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TREATMENT - Hormone blocking therapy
• Leutenising hormone- releasing hormone e.g
• Goserelin 3.6 mg SC depot q28d or 10.8 mg SC q3mo
• Leuprolide 7.5 mg IM depot q28d or 22.5 mg IM q3mo
• Selective estrogen receptor degrader e.g. fulvestrant
(Tong et al., 2018).
Note:
o SERM may affect a woman’s future fertility,
o luminal A subtypes are usually responsive to this therapy.
o Tamoxifen should be initiated shortly after surgery but after
completion of chemotherapy

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TREATMENT - Biological Treatment
• These are targeted drugs that can destroy certain types of
breast cancer. Examples are
• Lapatinib
• Trastuzumab
• Bevacizumab
• Chemotherapy plus trastuzumab (if indicated) is the strategy of
choice for ER-negative metastatic disease
• Patients who have tumors that overexpress for HER-2 are
preferably treated with trastuzumab as adjuvant or for
metastatic BC.
• Such patients may benefit from anthracycline -based
adjuvant therapy
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• But should not be given concurrently with trastuzumab
(Chisholm-Burns et al., 2013)..
 TREATMENT - Radiation therapy
• Radiation plays a key role not only in the treatment and
possible cure of cancer but also in palliative therapy.
• Together, surgery and radiation therapy may provide local
control of symptoms of the disease.
• Controlled doses of radiation is targeted at the tumor cells to
destroy the cancer.
• May be post-surgery or along with chemotherapy.
• Each session lasts few minutes at 3-5 sessions per week for 3-6
weeks depending on the aim of treatment and the extent of
cancer.
• Adverse effects include: fatigue, darkening and irritation of the
breast skin (Chisholm-Burns et al., 2013).
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TREATMENT - Managing Adverse Effects of
Cancer Chemotherapy
• Antiemetics that block serotonin and substance P
• Colony stimulating factors often are helpful in preventing
febrile neutropenia.
• Others are managed symptomatically with suitable
therapeutic agents:
• Cessation of menses with signs and symptoms of
menopause
• Deep vein thrombosis
• Leukemia
• Cardiomyopathy
• Hypersensitivity reactions, peripheral neuropathy, myalgias 28
and arthralgias (Chisholm-Burns et al., 2013).
ADVANCES IN TREATMENT
• Crizotinib -used for lung cancer- can be used in some breast
cancer patients with a particular genetic defect.
• Palcocicilib, ribocicilib for HR+ breast cancer in combination
with aromatase inhibitors.
• Buparlisib with lapatinib and MK-2206 with trastuzumab for
HER2 + breast cancer
• Talazoparib, olaparib, niraparib for triple negative breast
cancer (Tong et al., 2018).

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COMPLICATIONS
• Cancer related pain
• Bone complications
• Spinal compression
• Hypercalcemia
• Systemic dissemination to other organs

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REFERENCES
• Anampa, J., Makower, D., Sparano, J. A. (2015). Progress in agjuvant
chemotherapy for breast cancer: an overview. BMC Medicine.
13:195
• Boer K. (2002). Current trends in pharmacotherapy of breast
cancer. Orvolis Hetilap. 143(14):725-30.
• Chalasani, P., Kiluk, J. V. (Ed.) (2018). Breast Cancer. Retrieved Dec
17, 2018 from https://emedicine.medscape.com/article/1947145.
• Chisholm-Burns, M.A., Wells, B.G. and Schwinghammer, T.L.,
Malone, P.M., Kolesar, J.M., Dipiro J.T. (Eds) (2013).
Pharmacotherapy principles and practice. 3rd ed. McGraw-Hill.
• Omogbadegun, Z. O. (2013). Medicinal plants-basedd foods for
breast cancer treatment. An ethnobotanical survey and
digitization. Int. J. Med. Plant Altern. Med. 1(8):137-163.
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• Siegel, R. L., Miller, K. D., Jemal, A. (2017). Cancer statistics, 2017.
CA Cancer J Clin 67:7–30. doi:10.3322/caac.21387
REFERENCES
• Takimoto, C.H. and Calvo, E. (2005). Principles of oncoloigc
pharmacotherapy. Physicians Practice. Retrieved on Dec. 27,
2018 from
http://www.physicianspractice.com/articles/principles-oncolo
gic-pharmacotherapy
.
• Tong, C.W., Wu, M., Cho, W.C. and To, K.K., 2018. Recent
advances in the treatment of breast cancer. Frontiers in
oncology, 8.
• WHO 2019. Breast cancer. Retrieved Jan. 26, 2019 from
https://www.who.int/cancer/prevention/diagnosis-screening/
breast-cancer/en/
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