Aromatase Inhibitors

Type Dose Toxicities

Nonsteroidal

Anastrozole

Letrozole

1 mg daily PO

2.5 mg daily PO

Common toxicities: myalgias/

arthralgias, hot flashes,

osteoporosis

Steroidal

Exemestane 25 mg daily PO

PO, orally.

Source: Jones KL, Buzdar AU. A review of adjuvant hormonal therapy in breast

cancer. Endocr Relat Cancer. 2004;11:391; Buzdar AU, Howell A. Advances in

aromatase inhibitors: clinical efficacy and tolerability in the treatment of breast

cancer. Clin Cancer Res. 2001;7:2620.

inhibitors (AIs). Given this number of choices, menopausal status

of the patient is used to guide selection of therapy.

Traditionally, tamoxifen has been the gold standard for adjuvant hormonal therapy. Tamoxifen is a SERM, which works

by blocking estrogen from binding to the estrogen receptor. It

does not alter estrogen production. Tamoxifen has antiestrogenic activity in the breast, although it has estrogenic effects in

other areas such as bone.52,53 Tamoxifen can be used in both

premenopausal and postmenopausal women and is given 20 mg

orally daily for 5 years based on the data from the National Surgical Adjuvant Breast and Bowel Project B-14 trial.54,55 Tamoxifen

should be initiated after chemotherapy because it can antagonize

the antitumor activity of chemotherapy if given concurrently.56

Common toxicities associated with therapy are hot flashes and

vaginal discharge. More thrombosis, pulmonary embolisms, and

strokes can occur in patients (older than 50 years of age) receiving tamoxifen compared to placebo (risk ratio, 1.60, 3.19, 1.59,

respectively).4

Ovarian suppression is an alternative therapy for premenopausal patients as the ovaries are the largest source of

estrogen. This is typically achieved through the use of LH-RH

agonists. Surgery or radiation can also induce ovarian ablation;

however, surgery is irreversible but offers an immediate effect

where as radiation may offer an incomplete response and slower

onset.57 If a woman would like to maintain fertility throughout

chemotherapy, a thorough discussion with her physician should

occur. Studies with the use of LH-RH agents have been tested as

a means to preserve fertility but have shown mixed results.58

Postmenopausal patients also have the option of AI therapy.

Aromatase inhibitors inhibit the production of estrogen by preventing the conversion of androstenedione and testosterone to

estrone and estradiol. There are two classes of agents: nonsteroidal AIs (anastrozole and letrozole) and the steroidal AI,

exemestane. These agents are highly selective for the aromatase

enzyme and have less toxicity than tamoxifen and other hormonal agents. Aromatase inhibitors should only be used in postmenopausal women. If used in the premenopausal setting, initial

surges of estrogen occur due to the body’s compensation mechanisms (i.e., hypothalamic-pituitary axis) and negative feedback

loop. Table 93-5 provides a list of AIs.59–61 If used as single therapy,

AIs are given for 5 years.

The optimal hormonal therapy regimen for the adjuvant

setting has not been identified. In premenopausal women, the

options are 5 years of tamoxifen therapy plus or minus ovarian

suppression with an LH-RH agonist. If, after 2 to 3 years, the

patient is postmenopausal, then 2 to 3 years of an AI may be

given to complete a total of 5 years of therapy. If the patient is

postmenopausal at the beginning of adjuvant hormonal therapy,

an option would be to take an AI for 5 years. There have been

no prospective comparisons of the AIs with each other; therefore, any can be used as first-line treatment.60,61 Another clinical

option is 5 years of tamoxifen and then if the patient is postmenopausal after the end of 5 years, an additional 5 years of an

AI can be given. This was found beneficial in an extended study of

hormonal therapy (the BIG 1–98 trial). At the 2.4-year follow-up,

additional letrozole therapy was associated with a superior 4-year

diseasefree survival (93% with extended letrozole vs. 87% in the

tamoxifen arm; p <0.001).62 Table 93-6 lists adjuvant hormonal

therapy options.29

C.D. is premenopausal, so she would start with tamoxifen

therapy. If after 2 to 3 years of therapy, C.D. becomes postmenopausal, then she could continue the tamoxifen for a total

of 5 years or convert to an AI to complete a total of 5 years of

therapy. Because of her age, she will likely continue to be premenopausal after chemotherapy and be maintained on 5 years

of tamoxifen. If she completes 5 years of tamoxifen therapy and

is postmenopausal at that time, then extended use of an AI for

an additional 5 years would be recommended. Ovarian suppression with an LH-RH agonist can also be added because she is

premenopausal to chemically suppress her ovarian function.

TABLE 93-6

Overview of Adjuvant Hormonal Therapy

Premenopausal at time of

therapy initiation

(Patients can complete one

of 3 different options)

Option 1

Tamoxifen × 5 years ±

LH-RH agonist or ovarian

ablation

Option 2

If still premenopausal after 2–3 years of

tamoxifen therapy, complete a total of

5 years of tamoxifen.

If postmenopausal after 2–3 years:

A. Complete 5 years of tamoxifen followed

by 5 additional years of an AI

OR

B. Convert to an AI × 2–3 years for a total

of 5 years of hormonal therapy

Option 3

If still premenopausal after 5 years

of tamoxifen: Stop therapy

If postmenopausal after 5 years of

therapy give AI × 5 additional

years

Postmenopausal at time of 1. Any AI × 5 years OR

therapy initiation 2. Tamoxifen × 5 years OR

3. Tamoxifen × 2–3 years then AI to complete a total of 5 years OR

4. Tamoxifen × 4–6 years then an AI for 5 additional years

AI, aromatase inhibitor; LH-RH, luteinizing hormone–releasing hormone.

Source: National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Breast Cancer. v2. http://www.nccn.org. Accessed April 22, 2011.

2207Breast Cancer Chapter 93

METASTATIC BREAST CANCER

Treatment

CASE 93-4

QUESTION 1: T.R. is a 65-year-old, postmenopausal woman

diagnosed with breast cancer at the age of 48 years. At

the time of diagnosis she was premenopausal. She underwent surgery with a modified radical mastectomy and was

found to have a 1.5-cm invasive ductal carcinoma of the

right breast. She had two of ten lymph nodes positive.

Her breast cancer was ER-positive, PR-positive, and HER2-

negative. T.R. went on to complete adjuvant chemotherapy

with AC therapy for four cycles followed by weekly paclitaxel for 12 weeks. After completion of her chemotherapy,

she received 5 years of tamoxifen therapy. Ten years after

completing her therapy, she experiences pain in her right

arm and rib cage. A bone scan revealed metastatic breast

cancer. What would be an appropriate treatment regimen

for T.R. at this time?

Early-stage breast cancer is curable. However, if a patient

develops metastatic disease, the goal of treatment shifts from cure

to palliation and stabilization of disease. Treatment is offered to

improve quality of life and alleviate symptoms from treatment or

disease. The mean survival time after diagnosis of metastatic disease is approximately 2 to 4 years; however, this can range from

months to many years depending on the site of the metastases.63

The choice of therapy is based on the site of disease and other

factors that help guide therapy such as ER/PR status. Endocrine

therapy is more likely to be effective in patients with bone-only

disease whereas chemotherapy may be used when there is visceral disease (i.e., liver or lung). Patients with organ involvement

tend to have more rapidly growing disease that generally requires

therapy with a quicker onset of action such as chemotherapy.18

Common sites of metastases include liver, lung, brain, bone, and

lymph nodes.

In addition to systemic therapy (chemotherapy and/or hormonal therapy), the clinician needs to determine whether or not

local therapy (such as radiation or surgery) would be appropriate for a patient. Radiation therapy can be used to target painful

bone metastases, to prevent further tumor growth, and to relieve

pain. Surgery may be performed on bones with impending fractures, spinal cord compression, or brain metastases for palliation.

These modalities of treatment only affect the local site of disease,

so a combination of local and systemic therapy would need to be

administered to fully treat the patient. Chemotherapy generally

offers a much quicker onset of action compared to hormonal

therapy. If a patient is experiencing worsening symptoms such as

shortness of breath due to lung metastases or increased abdominal pain due to liver metastases, the use of chemotherapy may be

preferred over hormonal therapy.64 Disease recurrence greater

than 5 years after diagnosis illustrates a more indolent-growing

disease and is a favorable prognostic factor. Tumors with ER/PRpositive characteristics would also be considered a good prognostic factor. Once therapy is initiated, response to therapy should

be monitored periodically. Tumor markers such as CA.27.29 and

CA.15.3 are commonly monitored in metastatic breast cancer.

In addition, radiologic evaluation of disease progression (such

as a CT scan of the chest, abdomen, and pelvis or bone scan

depending on the sites of disease) would be conducted. A clinical examination in combination with radiologic tests and tumor

markers are assessed to determine response to therapy. Based on

T.R.’s metastatic bone disease and ER/PR-positive tumor characteristics, the use of hormonal therapy would be the most appropriate agent to initiate. T.R. received tamoxifen therapy in the

adjuvant setting. Because she progressed after taking tamoxifen

therapy, this would not be reinitiated. An AI would be started

because she is postmenopausal and should be continued until

there is evidence of progression of disease via radiologic findings

or increases in tumor markers.

CASE 93-4, QUESTION 2: T.R. is started on anastrozole

1 mg orally daily. What are the other hormonal agents that

can be used in the treatment of metastatic breast cancer?

Hormonal therapy in the metastatic setting can provide long

progressionfree survival in patients. If the patient responds for a

long period of time, the likelihood of response to another hormonal agent is high.64 A patient may take multiple hormonal

therapies before ever having to receive chemotherapy. As before,

the decision regarding which hormonal agent to use is based

on one’s menopausal status. If the patient is premenopausal

the options include tamoxifen and LH-RH agonists; however,

if the patient has received these agents in the adjuvant setting,

they would not be used again in the metastatic setting. Aromatase inhibitors are indicated for use in first-line therapy in

the metastatic setting. If an AI is chosen as the first-line agent

in the metastatic setting, use of another AI after progression

would include one from another category (i.e., nonsteroidal vs.

steroidal AI). For example, if anastrozole was used as first-line

therapy for metastatic disease, then when the patient progresses,

exemestane can be used.

Many other hormonal agents are available for use. The pure

antiestrogen, fulvestrant, is the only drug in a unique category

of agents. It exerts its mechanism via binding and blocking of the

estrogen receptor and downregulates the number of estrogen

receptors. Fulvestrant is administered as an intramuscular injection and is dosed 250 mg once a month. It is approved for use after

failure of tamoxifen therapy in the metastatic setting.65 This is an

alternative for patients with compliance issues due to its oncemonthly dosing. Other hormonal agents used in metastatic disease are megestrol acetate, progestins, and high-dose estrogens

(higher doses have been found to inhibit cancer cell growth).

These agents were used routinely before the approval of AIs.

Now they are reserved for use after multiple hormonal therapy

failures due to the toxicities associated with these therapies such

as weight gain, vaginal bleeding, and thromboembolic events.60

T.R. was started on anastrozole therapy. She could have been

initiated on any of the AIs. If her disease progresses, options

include sequential exemestane, then fulvestrant, and then other

agents such as megestrol acetate, high-dose estrogens, or androgens. The goal is to continue T.R. on multiple lines of hormonal therapy (as long as she is responding) before administering

chemotherapy.

Prevention of Skeletal Events

CASE 93-4, QUESTION 3: In addition to anastrozole therapy, what other supportive care medicines should be added

to T.R.’s regimen?

Patients with bone metastases are commonly treated with

bisphosphonate therapy to decrease the risk of skeletal-related

events (i.e., pathologic fractures, spinal cord compression, need

for surgery, or radiation to the bone). Bisphosphonates act by

inhibiting bone resorption. This ultimately will halt osteoclastic

activity leading to stabilization of bony involvement, prevention

of fractures, and reduction in calcium levels.66,67 Bisphosphonates used are pamidronate 90 mg intravenously (IV) for 2 hours

and zolendronic acid 4 mg IV for 15 minutes. Both of these can be

administered once a month. Bisphosphonates are typically well

tolerated although they may cause nausea, increased bone pain,

2208Section 17 Neoplastic Disorders

and fever. Reduced doses should be used in patients with underlying renal dysfunction. A more well-known but uncommon side

effect is osteonecrosis of the jaw.68 The mechanism by which

this occurs is not fully understood, but prevention is critical. If

dental extractions or surgery is needed, patients should not be

initiated on bisphosphonate therapy until these procedures are

completed. If these procedures are required after initiation of

therapy, an oral maxillofacial surgeon should be consulted.

A recently approved agent for use of prevention of skeletal

related events in solid tumors is the humanized monoclonal

antibody denosumab. This therapy offers a unique mechanism

of action targeted against RANK ligand, which is a mediator

in osteoclast activity. Inhibition of osteoclastic activity by denosumab reduces bone pathology in osseous metastases. Denosumab has been compared prospectively with zolendronic acid

in metastatic breast cancer patients and demonstrated significant

delays in and prevention of skeletal-related events.69 Denosumab

is administered as a subcutaneous injection and is given once a

month. It has similar toxicities to zolendronic acid and the dose

does not require adjustments for declining renal function. Denosumab has been added to the American Society of Clinical Oncology guidelines for the prevention of skeletal events in metastatic

breast cancer and other solid tumors.70 T.R. can start on bisphosphonate therapy with zolendronic acid 4 mg IV once a month

to help prevent skeletal-related events.

Progression of Disease

CASE 93-4, QUESTION 4: T.R. has a long progressionfree

survival on hormonal therapy. Over the course of 4 years,

she progresses on sequential anastrozole, then fulvestrant,

then exemestane, and then finally megestrol acetate. Each

time she has progressed, the progressionfree interval has

shortened. Follow-up staging tests reveal new liver lesions

measuring 1 cm × 1 cm and 2 cm × 1 cm. A CT scan of

the chest was negative. She is not currently experiencing

any symptoms of her disease. What should the treatment

course include now that T.R. is progressing on hormonal

therapy?

Because T.R. has progressed through multiple lines of hormonal therapy and the progressionfree interval has shortened

with each treatment course, chemotherapy would now likely

be the best option. Patients with a good performance status, little previous treatment, prolonged progressionfree intervals, and

limited metastatic disease are more likely to respond to further

treatment with chemotherapy.64 Chemotherapy is continued as

long as the person is receiving benefit and is tolerating toxicities

associated with treatment. If the disease progresses or the toxicities become intolerable, therapy should be changed or stopped.

Patients experiencing toxicities may be placed on chemotherapy

holiday until toxicities are resolved or until therapy is tolerable.

In the metastatic setting, the goal of therapy is stabilization of disease and palliation of symptoms. This is considered

when deciding what chemotherapy regimen to use. Sequential

(single agent) versus combination chemotherapy should be discussed. Combination chemotherapy is generally associated with

more toxicities than sequential; however, it provides improved

response rates.71 Patients with substantial symptoms from their

disease may initially be given combination therapy to rapidly

shrink the tumor. Combination therapies that have demonstrated

improvements in survival are docetaxel and capecitabine, paclitaxel and gemcitabine, and doxorubicin and paclitaxel. Based on

T.R.’s lack of symptoms, sequential therapy would be the best

option for her at this time. This would offer her less toxicity and

reserve other chemotherapeutic agents for the future.

TABLE 93-7

Commonly Used Chemotherapy Agents in the

Metastatic Setting

Sequential or single agent Doxorubicin, epirubicin

Liposomal doxorubicin, paclitaxel

Docetaxel, capecitabine

Vinorelbine, gemcitabine

Albumin-bound paclitaxel, eribulin

Combination chemotherapy FAC/CAF, FEC

AC EC

Doxorubicin/docetaxel CMF

Doxorubicin/paclitaxel, GT

Docetaxel/capecitabine

Ixabepilone/capecitabine

Single-agent chemotherapy +

trastuzumab

Docetaxel/trastuzumab TCH

Vinorelbine/trastuzumab

capecitabine/trastuzumab

If previously received

trastuzumab

Lapatinib/capecitabine

Trastuzumab + other first-line

agents

Trastuzumab/capecitabine

Trastuzumab/lapatinib

Single-agent therapy used

after failing standard

options listed here

Cyclophosphamide mitoxantrone

Cisplatin etoposide (oral)

Vinblastine fluorouracil

(continuous infusion)

Ixabepilone

A, doxorubicin; C, cyclophosphamide; E, epirubicin; F, fluorouracil; G,

gemcitabine; H, trastuzumab; M, methotrexate; T, paclitaxel.

Source: National Comprehensive Cancer Network. Clinical practice guidelines

in oncology. Breast Cancer. v2. http://www.nccn.org. Accessed April 22, 2011.

Chemotherapy selection is also based on the therapy received

in the adjuvant setting. Most individuals today will have received

an anthracycline and taxane chemotherapy. If the patient’s disease

recurs quickly after adjuvant therapy, the disease is considered

resistant to that treatment and different agents should be selected.

If a patient receives adjuvant paclitaxel and progresses on therapy,

there are data to support the use of docetaxel in the treatment of

metastatic disease because of the lack of cross-resistance between

taxanes.72

Previous toxicity is also considered when selecting therapy.

In patients with pre-existing neuropathies either from diabetes

or chemotherapy, taxanes may not be an appropriate choice

because these agents can also cause neuropathy. Additionally,

capecitabine may be chosen over intravenous chemotherapy

because this agent is administered orally. Table 93-7 provides

a list of commonly used agents in the metastatic setting. Clinical

trials are always an option for patients if they have a good performance status. Many clinical trials are available and should be

discussed with the patient if clinical trials are possible and available. Because T.R. has received an anthracycline and taxane agent

in the adjuvant setting, an agent such as capecitabine would be

an appropriate choice. This is an oral agent and also has the indication for first-line treatment of metastatic disease after failure

of anthracycline and taxane chemotherapy.

Biologic and Other Targeted Therapies

CASE 93-4, QUESTION 5: Would T.R. be a candidate for any

biologic therapy for the treatment of her metastatic breast

cancer?

Trastuzumab revolutionized the treatment of metastatic,

HER2-positive breast cancer. Now, other biologic therapies are

2209Breast Cancer Chapter 93

used in the metastatic setting. Trastuzumab is a fully humanized

monoclonal antibody that binds to the extracellular HER2 receptor and works via antigen dependent cellular cytotoxicity. When

chemotherapy alone was compared with chemotherapy plus

trastuzumab in HER2-positive, metastatic breast cancer, the addition of trastuzumab therapy significantly increased survival.39

This was the first study of its kind using biologic therapy

and demonstrating survival benefit in metastatic breast cancer.

Current practice is to continue the trastuzumab in patients who

progress on a chemotherapy regimen but switch to an alternative chemotherapy agent. Because T.R. does not have HER2-

positive breast cancer, therapy with trastuzumab would not be

warranted. Trastuzumab resistance can develop and numerous

studies are underway to identify new agents that may overcome

this resistance pattern.

Lapatinib is an oral tyrosine kinase inhibitor (small molecule)

that inhibits both the activity of HER2 and the epidermal growth

factor receptor. Lapatinib received approval based on a study

in which capecitabine was compared with capecitabine plus

lapatinib.73 This trial included patients whose disease had progressed during or after an anthracycline, taxane, and trastuzumab

therapy. Time to progression was statistically significantly better

with the combination therapy compared to capecitabine alone

(HR, 0.46; 95% confidence interval, 0.34–0.71; p <0.001).

After preclinical testing demonstrated synergistic effects of

lapatinib and trastuzumab together, the combination was studied

in patients with trastuzumab-refractory disease.74 The combination provided better progressionfree survival and clinical benefit

rates versus single-agent lapatinib therapy. Toxicities commonly

associated with lapatinib are diarrhea and rash. Concerns of cardiotoxicity associated with lapatinib have been closely monitored

in these trials. Because one of the mechanisms of lapatinib is

blockade of HER2 (like trastuzumab), there is concern regarding

its cardiotoxicity potential. Currently, data do not demonstrate

an increased risk of cardiac dysfunction with lapatinib; however,

long-term data are needed.75 Lapatinib’s indication includes use

in combination with capecitabine or combined with letrozole

therapy for metastatic breast cancer.

One concern with lapatinib is its inhibition of the cytochrome

P-450 (CYP) 3A4 and 2C8 isoenzymes. Because of this, when a

patient is initiated on therapy, a full review of medications should

occur to ensure no drug–drug interactions. Recommendations

are included in the package insert for use and dosing of lapatinib

with CYP3A4 inhibitors and inducers. With strong inhibitors,

the dose can be decreased to as low as 500 mg orally daily

and with strong inducers the dose can be increased gradually

from 1,250 mg orally daily to up to 4,500 mg orally daily.76 T.R.

would not receive lapatinib in combination with trastuzumab

or capecitabine because she does not have HER2-positive breast

cancer.

Bevacizumab, a recombinant humanized monoclonal antibody, inhibits vascular endothelial growth factor and, ultimately,

angiogenesis. In first-line treatment of metastatic breast cancer,

bevacizumab plus paclitaxel demonstrated significantly better

response rates and time to progression compared with paclitaxel

alone.77 Subsequent trials evaluating the benefit of bevacizumab

in this setting demonstrated similar results with improvements

in progressionfree survival, but showed no difference in overall

survival. Based on these results, the US Food and Drug Administration removed the indication for first-line use of bevacizumab

in combination with paclitaxel.78 Currently, bevacizumab is generally continued in patients who are receiving benefit or who are

on a clinical trial. This would not be an option for T.R. given the

lack of overall survival benefit.

Other unique targeted therapies are being evaluated in

metastatic breast cancer. Poly-ADP-ribose polymerase (PARP)

inhibitors potentially offer unique activity for patients with triple

negative breast cancers (ER/PR/HER2-negative disease). These

tumors are typically refractory to chemotherapy and difficult

to treat. PARP is an enzyme that repairs DNA breaks and is

overexpressed in triple-negative breast cancers. Hence, this class

of investigational inhibitors is expected to enhance the activity for cytotoxic therapies such as DNA-damaging agents. Initial studies have been promising and currently phase III trials are underway to evaluate the antitumor activity of PARP

inhibitors in the metastatic setting.79 Other agents in the pipeline

are mTOR (mammalian target of rapamycin) inhibitors, HSP90

(heat shock protein 90) inhibitors, multitargeted inhibitors of

vascular endothelial growth factor receptor, and platelet-derived

growth factor, and other monoclonal antibodies.80 At this time,

T.R. would be a candidate for a clinical trial with another targeted

therapy or to receive other cytotoxic chemotherapy agents used

in the metastatic setting.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT10e. Below are the key references

and website for this chapter, with the corresponding reference

number in this chapter found in parentheses after the reference.

Key References

Briest S, Stearns V. Chemotherapeutic strategies for advanced

breast cancer. Oncology (Williston Park). 2007;21:1325. (64)

Burnstein HJ et al. American Society of Clinical Oncology Clinical practice guideline: update on adjuvant endocrine therapy

for women with hormone receptor-positive breast cancer. J Clin

Oncol. 2010;28:3784. (61)

Carlson RW et al. Invasive breast cancer. J Natl Compr Canc Netw.

2011;9:136. (10)

Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).

Effects of chemotherapy and hormonal therapy for early breast

cancer on recurrence and 15-year survival: an overview of the

randomised trials. Lancet. 2005;365:1687. (35)

Fisher B et al. Tamoxifen for prevention of breast cancer: report

of the National Surgical Adjuvant Breast and Bowel Project P-1

study. J Natl Cancer Inst. 1998;90:1371. (4)

Jatoi I, Proschan MA. Randomized trials of breast conserving

therapy versus mastectomy for primary breast cancer: a pooled

analysis of updated results. Am J Clin Oncol. 2005;28:289. (28)

Lyman GH et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in earlystage breast cancer. J Clin Oncol. 2005;23:7703. (34)

Mayer EL, Burstein HJ. Chemotherapy for metastatic breast cancer. Hematol Oncol Clin North Am. 2007;21:257. (71)

Romond EH et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med.

2005;353:1673. (40)

Slamon DJ et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783. (39)

Tan SH, Wolff AC. Treatment of metastatic breast cancer:

chemotherapy. In: Harris JR et al, eds.Diseases of the Breast. 4th ed.

Philadelphia, PA: Lippincott Williams & Wilkins; 2009:877. (63)

Key Websites

National Comprehensive Cancer Network. Clinical practice

guidelines in oncology. Breast Cancer. v2. http://www.nccn.

org. Accessed April 22, 2011. (29)

94 Lung Cancer

Mark N. Kirstein, Robert A. Kratzke, and Arkadiusz Z. Dudek

CORE PRINCIPLES

CHAPTER CASES

1 Non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) together

account for more cancer-related deaths than any other malignancy for both men

and women. Smoking is the biggest risk factor, and is proportional to the number

of pack years. For former smokers, the risk for developing the disease decreases

over time, after smoking cessation.

Case 94-1 (Question 1)

2 Chances for survival are increased for those whose disease is detected early.

However, there are no effective screening methods for detecting early stage

disease in asymptomatic patients, although results from the National Lung

Screening Trial appear promising for improved survival.

Case 94-1 (Question 1)

3 The initial signs and symptoms vary according to location and stage of the disease.

Many patients are asymptomatic upon initial diagnosis, or signs and symptoms

may be masked by other concurrent conditions such as chronic obstructive

pulmonary disease.

Case 94-1 (Question 2),

Case 94-2 (Question 1)

4 Surgery, radiotherapy, and chemotherapy are all modalities used in the treatment

of NSCLC. Treatment decisions are individualized according to disease stage,

tumor histology (e.g., adenocarcinoma, squamous), presence or absence of

molecular marker mutations (e.g., epidermal growth factor receptor), performance

status, co-morbidities, and patient preference.

Case 94-1 (Questions 2, 3),

Case 94-2 (Questions 1–6)

5 SCLC tumors generally have a higher proliferation rate than NSCLC tumors. Hence,

chemotherapy and radiotherapy are the primary treatments. SCLC tumors tend to

grow more centrally than NSCLC tumors; therefore, surgical resection is usually not

performed.

Case 94-3 (Questions 3, 4)

6 Most NSCLC cytotoxic chemotherapy regimens are cisplatin-based or carboplatinbased doublets, which are given for 4 to 6 cycles. Targeted therapies are currently

limited to the treatment of some late-stage inoperable NSCLCs, but their use is

under investigation for patients diagnosed with earlier stages of the disease.

Case 94-1 (Question 4),

Case 94-2 (Questions 1–3)

7 Most SCLC cytotoxic chemotherapy regimens are cisplatin-based or

carboplatin-based doublets in combination with etoposide or sometimes

irinotecan if extensive stage disease. Investigations have not shown the utility for

targeted agents in treating this disease.

Case 94-3 (Questions 3, 4)

LUNG CANCER

Lung cancers may be referred to as non–small cell lung cancer

(NSCLC) or small cell lung cancer (SCLC), and although there

are many similarities between these two, treatments often differ.

Approximately 85% of lung cancers are classified as NSCLC and

the remaining are classified as SCLC. This chapter will initially

focus on the presentation, diagnosis, and treatment of NSCLC,

followed by a shorter section that describes SCLC.