BREAST STAGING

Staging
The American Joint Committee on Cancer (AJCC) staging system groups patients into 4 stages based
on tumor size (T), lymph node status (N), and distant metastasis (M). See Table 5, below.
Primary tumor (T)
Tumor size definitions are as follows:
Tx: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: (DCIS) Carcinoma in situ
Tis: (LCIS) Carcinoma in situ
Tis: Paget disease of the nipple with no tumor (Paget disease associated with a tumor is
classified according to the size of the tumor.)
T1: Tumor 2 cm or smaller in greatest diameter
T1mic: Microinvasion 0.1 cm or less in greatest dimension
T1a: Tumor >0.1 but not >0.5 cm in greatest diameter
T1b: Tumor >0.5 but not >1 cm in greatest diameter
T1c: Tumor >1 cm but not >2 cm in greatest diameter
T2: Tumor >2 cm but not >5 cm in greatest diameter
T3: Tumor >5 cm in greatest diameter
T4: Tumor of any size, with direct extension to (a) the chest wall or (b) skin only, as described
below
T4a: Extension to the chest wall, not including the pectoralis muscle
T4b: Edema (including peau dorange) or ulceration of the skin of the breast or satellite skin
nodules confined to the same breast
T4c: Both T4a and T4b
T4d: Inflammatory disease
Regional lymph nodes (N)
Regional lymph node definitions are as follows:
Nx: Regional lymph nodes cannot be assessed (eg, previously removed)
N0: No regional lymph node metastasis
N1: Metastasis in movable ipsilateral axillary lymph node(s)
N2: Metastasis in ipsilateral axillary lymph node(s) fixed or matted, or in clinically apparent
ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node
metastasis
N2a: Metastasis in ipsilateral axillary lymph nodes fixed to one another or to other
structures
N2b: Metastasis only in clinically apparent ipsilateral internal mammary nodes and in the
absence of clinically evident axillary lymph nodes
N3: Metastasis in ipsilateral infraclavicular or supraclavicular lymph node(s) with or without
axillary lymph node involvement, or clinically apparent ipsilateral internal mammary lymph
node(s) and in the presence of axillary lymph node
N3a: Metastasis in ipsilateral infraclavicular lymph node(s)
N3b: Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s)
N3c: Metastasis in ipsilateral supraclavicular lymph node(s)
Distant metastasis
Metastases are defined as follows:
Mx: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis
Table 5. TNM Staging System for Breast Cancer (Open Table in a new window)
Stage Tumor Node Metastases
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage IIA T0



T1



N1



N1



M0



M0



T2


N0


M0


Stage IIB T2



T3


N1



N0


M0



M0


Stage IIIA T0



T1



T2



T3


N2



N2



N2



N1-2


M0



M0



M0



M0


Stage IIIB T4



T4



T4


N0



N1



N2


M0



M0



M0


Stage IIIC Any T N3 M0
Stage IV Any T Any N M1
Five-year survival rates are highly correlated with tumor stage, as follows:
Stage 0: 99-100%
Stage I: 95-100%
Stage II: 86%
Stage III: 57%
Stage IV: 20%
This prognostic information can guide physicians in making therapeutic decisions. Pathologic review
of the tumor tissue for histological grade along with the determination of estrogen/progesterone
receptor status and HER2 status is necessary for determining prognosis.
Evaluation of lymph node involvement by sentinel lymph node biopsy or axillary lymph node
dissection has also been considered necessary for staging and prognosis, as recommended in the
2009 edition of the National Comprehensive Cancer Network (NCCN) breast cancer guidelines, but
the 2011 update modifies this recommendation. The 2011 NCCN breast cancer guidelines state that
lymph node evaluation is optional in the following cases:
Strongly favorable tumors
When no result would affect the choice of adjuvant systemic therapy
Elderly patients
Patients with comorbid conditions
The 2011 NCCN guidelines state that for staging, sentinel lymph node biopsy is preferred over
axillary lymph node dissection.
[11, 7]
.

Pengobatan kanker
Ada beberapa pengobatan kanker payudara yang penerapannya banyak tergantung pada stadium
klinik penyakit (Tjindarbumi, 1994), yaitu:
Mastektomi
Mastektomi adalah operasi pengangkatan payudara. Ada 3 jenis mastektomi (Hirshaut & Pressman,
1992):
Modified Radical Mastectomy, yaitu operasi pengangkatan seluruh payudara, jaringan
payudara di tulang dada, tulang selangka dan tulang iga, serta benjolan di sekitar ketiak.
Total (Simple) Mastectomy, yaitu operasi pengangkatan seluruh payudara saja, tetapi bukan
kelenjar di ketiak.
Radical Mastectomy, yaitu operasi pengangkatan sebagian dari payudara. Biasanya disebut
lumpectomy, yaitu pengangkatan hanya pada jaringan yang mengandung sel kanker, bukan
seluruh payudara. Operasi ini selalu diikuti dengan pemberian radioterapi. Biasanya
lumpectomy direkomendasikan pada pasien yang besar tumornya kurang dari 2 cm dan
letaknya di pinggir payudara.
Radiasi
Penyinaran/radiasi adalah proses penyinaran pada daerah yang terkena kanker dengan
menggunakan sinar X dan sinar gamma yang bertujuan membunuh sel kanker yang masih tersisa di
payudara setelah operasi (Denton, 1996). Efek pengobatan ini tubuh menjadi lemah, nafsu makan
berkurang, warna kulit di sekitar payudara menjadi hitam, serta Hb dan leukosit cenderung menurun
sebagai akibat dari radiasi.
Kemoterapi
Kemoterapi adalah proses pemberian obat-obatan anti kanker atau sitokina dalam bentuk pil cair
atau kapsul atau melalui infus yang bertujuan membunuh sel kanker melalui mekanisme kemotaksis.
Tidak hanya sel kanker pada payudara, tapi juga di seluruh tubuh (Denton, 1996). Efek dari
kemoterapi adalah pasien mengalami mual dan muntah serta rambut rontok karena pengaruh obat-
obatan yang diberikan pada saat kemoterapi.

There are 2 types of mammography examinations: screening and diagnostic. Screening
mammography is done in asymptomatic women.
Diagnostic mammography is performed in symptomatic women (eg, when a breast lump or nipple
discharge is found during self-examination or an abnormality is found during screening
mammography). This examination is more involved, time-consuming, and expensive than screening
mammography and is used to determine the exact size and location of breast abnormalities and to
image the surrounding tissue and lymph nodes. Women with breast implants or a personal history of
breast cancer will usually require the additional views used in diagnostic mammography.
Other uses of mammography in breast cancer
A ductogram, or galactogram, is sometimes helpful for determining the cause of nipple discharge. In
this specialized examination, a fine plastic tube is placed into the opening of the duct in the nipple. A
small amount of contrast medium is injected, which outlines the shape of the duct on a
mammogram and shows whether a mass is present inside the duct.
Treatment of Invasive Breast Cancer
Surgical treatment of invasive breast cancer may consist of lumpectomy or total mastectomy.In
breast cancer patients who have clinically negative nodes, surgery typically includes sentinel lymph
node dissection for staging the axilla. Go to Surgical Treatment of Breast Cancer for more
information on these topics. In addition to surgery, the use of radiation therapy, chemotherapy, or
both may be indicated.
Breast-conserving radiation therapy
The purpose of radiation therapy following breast-conserving surgery is to eradicate local subclinical
residual disease while reducing local recurrence rates by approximately 75%. Based on results from
several randomized controlled studies, radiation to the intact breast is considered standard of care,
even in the lowest-risk disease with the most favorable prognostic features.
There are 2 general approaches used to deliver radiation therapy: conventional external beam
radiotherapy (EBRT) and partial-breast irradiation (PBI). Whole-breast radiotherapy (WBRT) consists
of EBRT delivered to the breast at a dose of 50-55 Gy over 5-6 weeks. This is often followed by a
boost dose specifically directed to the area in the breast where the tumor was removed.
Common side effects of radiation therapy include fatigue, breast pain, swelling, and skin
desquamation. Late toxicity (lasting 6 mo or longer following treatment) may include persistent
breast edema, pain, fibrosis, and skin hyperpigmentation. Rare side effects include rib fractures,
pulmonary fibrosis, cardiac disease (left breast treatment), and secondary malignancies such as
radiation-induced sarcoma (0.5%).
Partial-breast irradiation is employed in early stage breast cancer following breast-conserving
surgery as a way of delivering larger fraction sizes while maintaining a low risk of late effects. Several
techniques that can deliver this therapy include interstitial brachytherapy (multiple catheters placed
through the breast) and intracavitary brachytherapy (a balloon catheter inserted into the
lumpectomy site [ie, MammoSite]).
Treatment is typically for 5 days, twice daily. These techniques have shown low local recurrence
rates comparable to EBRT in several nonrandomized studies.
The American Society of Breast Surgeons (ASBrS) recommends the following selection criteria when
considering patients for treatment with accelerated partial breast irradiation:
Age 45 years and older
Invasive ductal carcinoma or DCIS
Total tumor size (invasive and DCIS) 3 cm or smaller
Negative microscopic surgical margins of excision
Axillary lymph node/sentinel lymph node negative
Potential complications of partial-breast irradiation are catheter placement, followed by removal
secondary to inadequate skin spacing, infection, seroma, fibrosis, chronic pain, or disease
recurrence.
Postmastectomy radiation therapy
Clinical practice guidelines developed by ASCO along with several prospective, randomized clinical
trials recommend postmastectomy radiation therapy be performed using the following criteria:
Positive postmastectomy margins
Primary tumors larger than 5 cm
Involvement of 4 or more lymph nodes
Patients with more than 4 positive lymph nodes should also undergo prophylactic nodal radiation
therapy at doses of 4500-5000 cGy to the axillary and supraclavicular regions. For patients who
undergo axillary lymph node dissection and are found to have no lymph node involvement, axillary
radiation therapy is not recommended.
Meta-analyses have shown postmastectomy radiation therapy combined with regional nodal
radiation therapy significantly decreases the rate of local relapse and breast cancer mortality.
Currently, the benefit of radiation therapy for women with 1-3 positive axillary lymph nodes is
uncertain, and studies are ongoing.
Antineoplastic Agents
Class Summary
Various chemotherapy regimens are recommended for the treatment of breast cancer. Common
regimens include docetaxel, cyclophosphamide, doxorubicin, carboplatin, methotrexate, and
trastuzumab, among others.
Docetaxel (Taxotere)

Docetaxel is indicated for use in combination with doxorubicin and cyclophosphamide for adjuvant
treatment of operable node-positive breast cancer. It is also indicated for locally advanced or
metastatic breast cancer after failure of prior chemotherapy. It is a semisynthetic taxane, a class of
drugs that inhibits cancer cell growth by promoting assembly and blocking the disassembly of
microtubules, thereby preventing cancer cell division, leading to cell death.
Carboplatin

Carboplatin is an analog of cisplatin. This is a heavy metal coordination complex that exerts its
cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand
and intrastrand DNA cross-links and inhibition of DNA replication. It binds to protein and other
compounds containing the SH group. Cytotoxicity can occur at any stage of the cell cycle, but the cell
is most vulnerable to the action of these drugs in the G1 and S phases. It has the same efficacy as
cisplatin, but with a better toxicity profile. The main advantages over cisplatin include less
nephrotoxicity and ototoxicity, not requiring extensive prehydration, and less likelihood of inducing
nausea and vomiting; however, it is more likely to induce myelotoxicity.
Doxorubicin (Liposomal)

Doxorubicin is a cytotoxic anthracycline that inhibits topoisomerase II and produces free radicals,
which may cause destruction of DNA. It blocks DNA and RNA synthesis by inserting between
adjacent base pairs and binding to the sugar-phosphate backbone of DNA, which causes DNA
polymerase inhibition. It binds to nucleic acids, presumably by specific intercalation of the
anthracycline nucleus with the DNA double helix. It is also a powerful iron chelator. The iron-
doxorubicin complex induces production of free radicals that can destroy DNA and cancer cells.
Maximum toxicity occurs during the S phase of the cell cycle.
Capecitabine (Xeloda)

Capecitabine is a pyrimidine analog, which, in combination with docetaxel, is indicated for
metastatic breast cancer after the failure of prior anthracycline-containing chemotherapy.
Monotherapy with capecitabine is indicated for the treatment of patients with metastatic breast
cancer resistant to both paclitaxel and an anthracyclinecontaining chemotherapy regimen or
resistant to paclitaxel and for whom further anthracycline therapy is not indicated.
[17]

Paclitaxel

Paclitaxel is indicated for adjuvant treatment of node-positive breast cancer (ie, administered
sequentially to doxorubicin-containing combination chemotherapy). Dose-dense regimens (ie, more
frequent administration) are currently being studied and resulting disease-free interval examined.
Mechanisms of action are tubulin polymerization and microtubule stabilization, which, in turn,
inhibit mitosis and may result in the breakage of chromosomes.
Gemcitabine (Gemzar)

Gemcitabine is a pyrimidine analog that is metabolized intracellularly to an active nucleotide. It
inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation
into DNA. It is cell-cycle specific for the S phase. Gemcitabine, in combination with paclitaxel, is
indicated as a first-line treatment for metastatic breast cancer after the failure of prior
anthracycline-containing adjuvant chemotherapy (unless anthracyclines were clinically
contraindicated).
Cyclophosphamide

Cyclophosphamide is chemically related to nitrogen mustards. It is indicated for use in patients with
carcinoma of the breast. It is activated in the liver to its active metabolite, 4-
hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none type
of reaction. As an alkylating agent, the mechanism of action of the active metabolites may involve
cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells.
Methotrexate (Trexall)

Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA
synthesis and cell reproduction in malignant cells. Methotrexate is indicated alone or in combination
with other anticancer agents for the treatment of breast cancer.
Epirubicin (Ellence)

Epirubicin is indicated as a part of adjuvant therapy in patients with evidence of axillary-node tumor
involvement following resection of primary breast cancer.
[18]
It is a cell cycle phase inhibitor
nonspecific anthracycline derivative of doxorubicin with maximum cytotoxic effects on the S and G2
phases of the cell cycle.
Vinorelbine (Navelbine)

Vinorelbine is a semisynthetic vinca alkaloid that inhibits tubulin polymerization during the G2 phase
of cell division, thereby inhibiting mitosis.