26: Cancer and Oral Care of the Cancer Patient

Chapter 26

Cancer and Oral Care of the Cancer Patient

Collectively, all cancers combined account for about 23% of deaths in the United States, thereby placing cancer second only to heart disease as a leading cause of death.< ?xml:namespace prefix = "mbp" />1 Cancer is a major public health problem in the United States and other developed countries. Concordant with improvements in health and medical care resulting in increased longevity, the prevalence of cancer has increased over the past 50 years. Currently, one in four deaths in the United States is due to cancer. In 2006, the probability of developing cancer from birth to death in the United States in men was 46% and in women, 38%.2,3

A total of 1.5 million new cancer cases and over 600,000 deaths from cancer are expected in the United States in 2011 (Table 26-1). When deaths are aggregated by age, cancer has surpassed heart disease as the leading cause of death for those younger than age 85 since 1999.1,2

TABLE 26-1 Estimated New Cancer Cases and Deaths by Sex, United States, 2010*

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The death rate from all cancers combined has decreased slightly in the past 10 years.1,2 The mortality rate has also continued to decrease for the three most common cancer sites in men (lung and bronchus, colon and rectum, and prostate) and for breast and colon and rectum cancers in women.2 Lung cancer mortality among women continues to increase slightly. As with many diseases, ethnic disparities exist. In analyses by race and ethnicity, African American men and women have 40% and 18% higher death rates from all cancers combined than white men and women, respectively. Cancer incidence and death rates are lower in other racial and ethnic groups than in whites and African Americans for all sites combined and for the four major cancer sites. However, these groups generally have higher rates for stomach, liver, and cervical cancers than those reported for whites. Furthermore, minority populations are more likely than whites to be diagnosed with advanced-stage disease. Progress in reducing the burden of suffering and death from cancer can be accelerated by applying existing cancer control knowledge across all segments of the population.2,3

Because patients diagnosed with cancer are experiencing increased survival as a result of improved diagnostics and advances in antineoplastic therapy, an increased likelihood exists of dentists treating patients in various phases of cancer therapy. For optimum oral health, the dentist should be an integral part of the cancer patient’s health care team. The characteristic clinical course, cancer progression status, treatment modalities, the location of cancer therapy (hospital or outpatient facility), and the likely outcome all will affect the dental treatment plan. Maintenance of proper oral hygiene is critical for limiting local and systemic complications associated with chemotherapy, radiation therapy, and marrow and stem cell transplantation. In addition, dentists have the unique opportunity to reduce the risk of cancer by providing advice regarding cancer screening, a healthy diet, counseling patients as appropriate regarding smoking cessation and risks associated with alcohol consumption, and performing cancer screening procedures.

This chapter focuses on common cancers that may affect patients who require dental care. No attempt is made here to include all cancers; instead, an overview of cancer is presented first, followed by a discussion of common cancers, along with relevant considerations regarding oral care of patients with cancer. A discussion of lymphoma and leukemia can be found in Chapter 23.

Definition and Scope of the Problem

Cancer is characterized by uncontrolled growth of aberrant neoplastic cells.4 Cancerous cells kill by destructive invasion of tissues—that is, direct extension and spread to distant sites by metastasis through blood, lymph, or serosal surfaces. Malignant cells arise from genetic and acquired mutations, chromosomal translocations, and over- or underexpression of factors (oncogenes, growth factor receptors, signal transducers, transcription factors) that cause cells to lose their ability to regulate deoxyribonucleic acid (DNA) synthesis and the cell cycle. Cellular abnormalities of malignancy result in three common features: uncontrolled proliferation, ability to recruit blood vessels (i.e., neovascularization), and ability to spread.4

Epidemiology: Incidence and Prevalence

Figure 26-1 indicates the most common cancers expected to occur in men and women in 2010.1,2 Among men, cancers of the prostate, lung and bronchus, and colon and rectum account for more than 56% of all newly diagnosed cancers. In women the most common cancers are breast, lung, colon, and uterine.3

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FIGURE 26-1 Ten leading cancer types in estimated new cancer cases and deaths, by gender, United States, 2006. Indicated are the most common cancers that were expected to occur in men and women in 2006. Among men, cancers of the prostate, lung and bronchus, and colon and rectum account for more than 56% of all newly diagnosed cancers. Prostate cancer alone accounts for about 33% (234,460) of incident cases in men. On the basis of cases diagnosed between 1995 and 2001, an estimated 91% of new cases of prostate cancer were expected to be diagnosed at local or regional stages, for which relative 5-year survival approaches 100%.

(From Jamal A, et al: Cancer statistics, 2010, CA Cancer J Clin 60;277-300, 2010.

Etiology and Prevention

Carcinogenesis is a complex multistep process that involves the accumulation of mutations and the loss of regulatory control over cell division, differentiation, apoptosis, and adhesion4 (Figure 26-2). The process originates at the level of gene and cell cycle control, either by a hereditary mutation, acquired mutation or inappropriate expression of a transcription factor. Some syndromes which predispose individuals to cancer can be seen in Table 26-2.

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FIGURE 26-2 Carcinogenesis: pathologic sequence in gastrointestinal mucosa. Examples in colon and oral mucosa.

(Adapted from Jänne PA, Mayer RJ: Chemoprevention of colorectal cancer, N Engl J Med 342:1960-1968, 2000.)

TABLE 26-2 Syndromes of Inherited Cancer Predisposition in Clinical Oncology Syndrome

Syndrome Mode of Inheritance Gene(s)
Hereditary Breast Cancer Syndromes
Hereditary breast and ovarian cancer syndrome Dominant BRCA1
BRCA2
Li-Fraumeni syndrome Dominant TP53
Cowden’s syndrome Dominant PTEN
Bannayan-Riley-Ruvalcaba syndrome Dominant PTEN
Hereditary Gastrointestinal Malignancies
Hereditary nonpolyposis colon cancer Dominant MLH1
MLH2
MSH6
Familial polyposis Dominant APC
Hereditary gastric cancer Dominant CDH1
Juvenile polyposis   SMAD4/DPC4
BMPR1A
Peutz-Jeghers syndrome Dominant STK11
Hereditary melanoma–pancreatic cancer syndrome Dominant CDKN2A
Hereditary pancreatitis Dominant PRSS1
Turcot’s syndrome Dominant APC
MLH1
PMS2
Familial gastrointestinal stromal tumor Dominant KIT
Genodermatoses With Cancer Predisposition
Melanoma syndromes Dominant CDKN2A
CDK4
CMM
Basal cell cancer, Gorlin’s syndrome Dominant PTCH
Cowden’s syndrome Dominant PTEN
Neurofibromatosis 1 Dominant NF1
Neurofibromatosis 2 Dominant NF2
Tuberous sclerosis Dominant TSC1
TSC2
Carney’s complex Dominant PRKAR1A
Muir-Torre syndrome Dominant MLH1
MSH2
Xeroderma pigmentosum Recessive XPA,B,C,D,E,F,G
POLH
Rothmund-Thomson syndrome Recessive RECOL4
Leukemia/Lymphoma Predisposition Syndromes
Bloom’s syndrome Recessive BLM
Fanconi’s anemia Recessive FANCA,B,C
FANCA,D2
FANCE,F,G
FANCL
Ataxia-telangiectasia Recessive ATM
Shwachman-Diamond syndrome Recessive SBDS
Nijmegen breakage syndrome Recessive NBS1
Canale-Smith syndrome Dominant FAS
FASL
Wiskott-Aldrich syndrome X-linked recessive WAS
Common variable immune deficiency Recessive  
Severe combined immune deficiency X-linked recessive IL2RG
  Recessive ADA
JAK3
RAG1
RAG2
IL7R
CD45
Artemis
X-linked lymphoproliferative syndrome X-linked recessive SH2D1A
Genitourinary Cancer Predisposition Syndromes
Hereditary prostate cancer Dominant HPC1
HPCX
HPC2/ELAC2
PCAP
PCBC
PRCA
Simpson-Golabi-Behmel syndrome X-linked recessive GPC3
von Hippel–Lindau syndrome Dominant VHL
Beckwith-Wiedemann syndrome Dominant CDKN1C
NSD1
Wilms’ tumor syndrome Dominant WT1
Wilms’ tumor, aniridia, genitourinary abnormalities, mental retardation (WAGR) syndrome Dominant WT1
Birt-Hogg-Dub? syndrome Dominant FLCL
Papillary renal cancer syndrome Dominant MET,PRCC
Constitutional t(3;8) translocation Dominant TRCB
Hereditary bladder cancer Sporadic  
Hereditary testicular cancer Possibly X-linked  
Rhabdoid predisposition syndrome Dominant SNF5INI1
Central Nervous System/Vascular Cancer Predisposition Syndromes
Hereditary paraganglioma Dominant SDHD
SDHC
SDHB
Retinoblastoma Dominant RB1
Rhabdoid predisposition syndrome Dominant SNF5/INI1
Sarcoma/Bone Cancer Predisposition Syndromes
Multiple exostoses Dominant EXT1
EXT2
Leiomyoma/renal cancer syndrome Dominant FH
Carney’s complex Dominant PRKAR1A
Werner’s syndrome Recessive WRN
Endocrine Cancer Predisposition Syndromes
Multiple endocrine neoplasia 1 Dominant MEN1
Multiple endocrine neoplasia 2 Dominant RET
Familial papillary thyroid cancer Dominant Multiple loci

Adapted from Garber JE, Offit K: Hereditary cancer predisposition syndromes, J Clin Oncol 23:276-292, 2005.

The aggregation of cancer in a family can be due to genetic or nongenetic causes, the former through mendelian (single-gene mutation) or nonmendelian (polygenic or multifactorial) inheritance of genes that predispose to cancer and the latter related to common exposure to carcinogenic agents or lifestyle, or simple coincidence. The modern understanding of familial aggregation of cancer has required increasingly sophisticated epidemiologic and statistical methods in combination with genetic concepts and technologies.4

Although mendelian inheritance accounts for a small minority of all cancers, mutations that predispose to cancer have provided some of the most penetrating insights into the understanding of the genetic basis of normal as well as abnormal development; these mutations manifest the classical recessive or dominant modes of inheritance. Nonmendelian inheritance, which also plays a major role in the overall incidence of cancer, has been more difficult to characterize. In addition, the interaction of mutated genes with the environment adds another level of complexity in deciphering the role of genetics of cancer in individual patients as well as in families.4 Some of the genetic associations with cancer are shown in Table 26-2.

At least three to six somatic mutations are needed to transform a normal cell into a malignant cell. Acquired mutations can arise from exposure to hazardous chemicals and pathogens that lead to activation of oncogenes, inactivation of tumor suppressor genes (pRb and TP53), and chromosomal abnormalities (translocations, deletions, insertions). The accumulation of these abnormalities leads to a cell that becomes functionally independent and aggressive. Natural killer cells provide surveillance for cancerous cells. Reduction in numbers or function of natural killer cells, which occurs during immunosuppression, increases the risk for cancer.5

National efforts currently focus on the reduction or elimination of factors known to be associated with cancer. Recommendations from the American Cancer Society (ACS) are to minimize exposure to tobacco smoke and to environmental and occupational carcinogens (e.g., asbestos fibers, arsenic compounds, chromium compounds, pesticides); decrease intake of fat and exposure to ultraviolet light; moderate the intake of alcohol; obtain an adequate intake of dietary fiber and antioxidants (vitamins C and E, selenium); and perform moderate levels of physical activity.5

Pathophysiology and Complications

The loss of regulatory control in a cell destined to become a cancer cell results in a series of pathologic changes that eventuate in hyperproliferative epithelium, dysplasia, and finally carcinoma. Dysplastic tissue is characterized by atypical cell proliferation, nuclear enlargement, failure of maturation, and differentiation short of malignancy (see Figure 26-2).

Cytogenetic studies of various leukemias established four cardinal attributes of genetic change in cancer: (1) Specific or nonrandom chromosomal changes may characterize individual cancer types; (2) tumor genomes are genetically unstable and subject to continuing change, a feature now recognized as genomic instability; (3) all cells in a given tumor trace back to a single progenitor cell and therefore are clonal; and (4) tumor progression often is associated with additional specific or nonrandom chromosomal changes, presumably “selected” from the genomic instability, in subpopulations of tumor cells that lead clonal diversity and evolution. Chromosomal changes are of many types, the most common being gain of an entire chromosome (aneuploidy) or a region of it (duplication), loss of an entire chromosome (monosomy) or a region of it (deletion), translocation or inversion (rearrangement), and amplification (Figure 26-3).

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FIGURE 26-3 Common cytogenetic changes in cancer. The chromosome (at metaphase) is traditionally distinguished by its short and long arms separated by a centromere. Stylized bands (dark and light stripes along the length of the chromosome) produced by special treatments are also shown. The abnormality (right) and the corresponding normal image of the chromosome are illustrated in each panel. A, Gain of a chromosome leading to aneuploidy. B, Deletion of a chromosomal segment from one of the two homologues. C, Translocation showing exchange of segments between nonhomologous chromosomes. D, Amplification, with an increase in a region of a chromosome by replicating many times in place.

(From Goldman L, Ausiello D, editors: Cecil textbook of medicine, ed 23, Philadelphia, 2008, Saunders.)

Malignant cells exhibit antigenic, karyotypic, biochemical, and membrane changes that cause loss of contact inhibition, changes in chromosomal morphology, and increased permeability. Malignant tumors lack cell cycle control and replicate rapidly, becoming clinically detectable after about 30 cell doublings, when the mass contains about 109 cells (1 g). A three-log increase to 1012 cells produces a tumor that weighs 1 kg and often is lethal. After reaching clinically detectable size, tumors slow in growth as they reach anatomic boundaries and begin to outgrow their blood supply. Malignant tumors overcome the limitation of anatomic boundaries by losing cell adherence and by metastasizing. Metastasis is a distinct form of cancerous spread that occurs when malignant cells enter blood or lymphatic vessels and travel to distant sites. Metastasis is related to factors produced by tumors cells that allow individual cells to invade tissues and endothelium. It often results in end-organ failure and death.5

Clinical Presentation

Screening

Each year the ACS publishes a summary of its recommendations for early cancer detection. Obviously, the earlier any form of cancer is diagnosed, the more expeditiously and effectively it can be treated in order to minimize adverse outcomes: morbidity and mortality.

Table 26-3 outlines the most recent ACS recommendations for early cancer detection for several cancers. Further information can be found at cacancerjournal.org.

TABLE 26-3 Screening Recommendations of the American Cancer Society

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Signs and Symptoms

Cancers often manifest as a palpable mass that increase in size over time. Preceding the development of the tumor are subtle changes that are dependent on the anatomic site involved and the cell type of origin. Initial features can include a change in surface color, a lump, enlarged lymph node, or altered organ function. Symptoms include pain and paresthesia. Tumors permitted to increase in size often result in a reddened epithelial surface (due to increased blood vessels) that ulcerates.6

Staging

Most cancers are assigned a stage (I, II, III, or IV) by the medical team on the basis of the size of the tumor and how far it has spread (Box 26-1). Generically speaking, stage I disease is localized and confined to the organ of origin. Stage II disease is regional, affecting nearby structures. Regional head and neck lymph node anatomy can be seen in Figure 26-4. Stage III disease extends beyond the regional site, crossing several tissue planes, and stage IV disease is widely disseminated. This system often is supplemented by detailed and specific staging systems developed for particular cancers and generally does not apply to leukemia (because leukemia is a disease of the blood cells that does not usually form a solid mass or tumor). The tumor-node-metastasis (TNM) system frequently is used for this purpose (see Box 26-1). The patient’s prognosis depends in large part on the stage of disease at the time of diagnosis.6

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Box 26-1

International Tumor-Node-Metastasis (TNM) System of Classification and Staging of Oral Carcinomas

T: Tumor Size

TIS, carcinoma in situ

T1, tumor up to 2 cm in size

T2, tumor >2 cm up to 4 cm in size

T3, tumor >4 cm in size

T4, massive tumor with deep invasion into bone, muscle, skin

Adapted from Sobin L, Gospodarowicz M, Wittekind C, editors: UICC TNM classification of malignant tumours, ed 7, Hoboken, NJ, 2010, Wiley-Blackwell.

N: Regional Lymph Node Involvement

N0, no palpable nodes

N1, single, homolateral palpable node up to 3 cm in diameter

N2, single, homolateral palpable node, 3 to 6 cm or multiple, homolateral nodes, none >6 cm

N3, single or multiple, homolateral nodes, one >6 cm, or bilateral nodes (stage each side of neck), or contralateral nodes

M: Metastases

M0, no known distant metastasis

M1, distant metastasis—PUL (pulmonary), OSS (osseous), HEP (liver), BRA (brain)

Stage Classification

0 (carcinoma in situ) TIS, N0, M0
I T1, N0, M0
II T2, N0, M0
III T3, N0, M0 or T1, T2 or T3, N1, M0
IVA T4, N0, M0 or T4, N1, M0 or any T, N2, M0
IVB Any T, N3, M0
IVC Any T, any N, M1

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FIGURE 26-4 Regional lymph node anatomy.

(From Fehrenbach MJ, Herring SW: Illustrated anatomy of the head and neck, ed 4, St. Louis, 2012, Saunders.)

Laboratory Findings

The diagnosis of cancer is dependent on microscopic examination of an adequate sample of tissue taken from the lesion (Box 26-2). Tissue can be obtained by cytologic smears, needle biopsy, or incisional or excisional biopsy. Cells also can be subjected to flow cytometry, chromosomal analyses, in situ hybridization, or other molecular procedures to identify specific cancer markers, ploidy, and DNA analysis. Serum tumor markers such as carcinoembryonic antigen (CEA) for colorectal carcinoma (CA 15-3 or CEA in breast cancer and CA 125 for ovarian cancer) have low sensitivity for the detection of early-stage cancers but are useful in monitoring disease progression and response to therapy.

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Box 26-2 Microscopic Criteria for Malignancy

Cytoplasm Scant cytoplasm, increased nucleus to cytoplasm ratio, tight molding of cytoplasmic membrane around nucleus

Nucleus Enlargement with variation in size, irregular membrane with sharp angles, hyperchromasia, irregular chromatin distribution with clumping, prominent nucleoli, abundant or abnormal mitotic figures

Relationships Variation in cell size and shape, abnormal stratification, decreased cohesiveness

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Medical Management

Treatment strategies for cancer are based on eliminating fast multiplying cancer cells without killing the host. Therapeutic modalities include surgery; irradiation (by external beam or implants); regimens based on cytotoxic, chemotherapeutic, and endocrine drugs; and possibly stem cell or bone marrow transplantation. Surgery often is used when anatomy permits to debulk a tumor or if the cancer is limited in size. Radiation therapy (often at doses greater than 50 grays [Gy]7) kills cells by damaging cancer cell DNA and chromosomes needed for cell replication and is used when the tissue cannot be excised and when cells are most susceptible to this form of therapy. Chemotherapeutic agents are most effective against rapidly growing tumors by adversely affecting the DNA synthesis or protein synthesis of cancerous cells. A wide range of cancer chemotherapeutic compounds exist. They are divided into several categories: alkylating agents, antimetabolites, hormones, antibiotics, mitotic inhibitors, and miscellaneous drugs (Table 26-4). Tumoricidal efficacy is gained with use of these various agents in combination. High-dose multidrug protocols are employed in hospital settings to induce myelosuppression for patients with leukemia, lymphoma (see Chapter 23), and more recently, breast cancer who are scheduled to undergo bone marrow transplantation. Opportunistic infections are a major concern during the myelosuppressive period. Patients who receive outpatient chemotherapy are administered a lower-dose regimen on a 3- to 4-week schedule and are at lower risk for opportunistic infections.8

TABLE 26-4 Chemotherapy Drugs of Choice for Common Cancers

Cancer Drugs of Choice
Breast Risk reduction: Tamoxifen
Adjuvant: Doxorubicin + cyclophosphamide ± fluorouracil followed by paclitaxel; cyclophosphamide + methotrexate + fluorouracil; tamoxifen for receptor-positive and hormone-responsive tumors
Metastatic: Doxorubicin + cyclophosphamide ± fluorouracil; cyclophosphamide + methotrexate + fluorouracil
Tamoxifen or toremifene for receptor-positive and/or hormone-responsive tumors
Paclitaxel + trastuzumab for tumors that overexpress HER2 protein
Cervix Locally advanced: Cisplatin ± fluorouracil
Metastatic: Cisplatin; ifosfamide with mesna; bleomycin + ifosfamide with mesna + cisplatin
Colorectal Adjuvant: Fluorouracil + leucovorin
Metastatic: Fluorouracil + leucovorin + irinotecan
Head and neck Cisplatin + fluorouracil or paclitaxel
Kaposi sarcoma Liposomal doxorubicin or daunorubicin; doxorubicin + bleomycin + vincristine
Leukemia and lymphoma See Table 24-2
Liver Hepatic intraarterial floxuridine, cisplatin, doxorubicin or mitomycin
Lung
Non–small cell Paclitaxel + cisplatin or carboplatin; cisplatin + vinorelbine; gemcitabine + cisplatin; cisplatin or carboplatin + etoposide (PE)
Small cell
Melanoma Adjuvant: Interferon alfa
Metastatic: Dacarbazine
Multiple myeloma Melphalan or cyclophosphamide + prednisone; vincristine + doxorubicin (Adriamycin) + dexamethasone (VAD)
Prostate Gonadotropin-releasing hormone (GnRH) agonists (leuprolide or goserelin) ± antiandrogen (flutamide, bicalutamide, or nilutamide)
Renal Interleukin-2

Adapted from Drugs for cancer, Med Lett Drugs Ther 42:83-92, 2000.

Breast Cancer

Breast cancer is the most common type of cancer in the United States, with 98% of cases occurring in women. In 2010, approximately 207,000 cases of breast cancer were reported in the United States, with about 40,000 persons dying of the disease in that year.2 The incidence increases with age. Risk factors include early menarche, late menopause, and nulliparity (women who do not bear children). All breast cancers are the result of somatic genetic abnormalities. The most important risk factor of breast cancer is family history of the disease with 5% to 10% of cases arising in high-risk families. The most common mutations identified in breast cancer cells are in the BRCA1 and BRCA2 genes. These mutations confer a 50% to 85% lifetime risk of breast cancer. Abnormalities also have been identified in genes (bcl-2, c-myc, c-myb and TP53) and gene products (Her2/neu and cyclin D1) that regulate the cell cycle and DNA replication. Gonadal steroid hormones, growth factors, and various chemokines (such as IL-6) influence the behavior and dissemination of the disease. Cancer in one breast increases the risk for cancer development in the other.7,9,10

Breast cancer often is detected as a lump in the breast with or without nipple discharge, breast skin changes and breast pain. Mammography detects the mass in only 75% to 85% of patients (Figure 26-5). Although mammography recently has been controversial, it is still a valuable screening technique as considered by the ACS.11 In a small percentage of patients, the first sign is an axillary mass. Diagnosis is made from a tissue core biopsy of breast tissue. Most breast cancers are infiltrating ductal carcinomas, whereas a smaller percentage of tumors are infiltrating lobular carcinomas, medullary carcinomas, mucinous carcinoma, or tubular carcinoma. Metastasis occurs after the cancer becomes clinically detectable and is primarily to regional lymph nodes and within the chest wall, bone, lung, and liver.12

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FIGURE 26-5 Mammogram showing a radiodense area in the breast suggestive of a malignancy that should be recommended for biopsy.

(Courtesy A.R. Moore, Lexington, Kentucky.)

Treatment of breast cancer depends on the histologic type of cancer and stage. Cellular markers such as the Her2/neu molecule (target of drug herceptin) and the sodium-iodide symporter (NIS) aid in the diagnosis and treatment planning. Lumpectomy (when the tumor is less than 5 cm) or lumpectomy plus radiotherapy is preferred over radical mastectomy. Axillary node dissection is performed if the regional sentinel node is positive for malignancy. Hormone therapy (tamoxifen) and chemotherapy combined with local therapy is recommended when invasive carcinoma exceeding 1 cm in diameter or axillary lymph nodes are positive. The combination of fluorouracil, doxorubicin, and cyclophophamide usually is administered for 4 to 6 months, given at 3- to 4-week intervals. At present, metastatic breast cancer is incurable. Accordingly, the ACS recommends a mammogram and professional clinical examination every year for women 40 years of age and older (Box 26-3; see also Table 26-3). Women 20 to 39 years of age should have a professional breast examination at least every 3 years. Breast self-examination is an option for women starting in their 20s. The American Geriatrics Society recommends mammography every 2 or 3 years for healthy women between the ages of 65 and 85.12

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Box 26-3

American Cancer Society Recommendations for Early Breast Cancer Detection

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Cervical Cancer

Cancer of the uterine cervix occurred in nearly 12,000 women in the United States in 2010, and more than 4000 women died of the disease.8 Cervical cancer is relatively uncommon in developed countries because of the intensive screening programs in place. Since the widespread use of screening Papanicolaou (Pap) smears, which detect asymptomatic cancerous precursor lesions at early stages, the incidence of cervical cancer has decreased dramatically, from 32 cases per 100,000 women in the 1940s to 8.3 cases per 100,000 women at present. However, approximately 30% of these patients die of the disease within 5 years, and the death rate for African Americans is more than twice the national average.13

Human papillomaviruses (HPVs), which are epitheliotropic sexually transmitted DNA viruses, are the major etiologic agent of cervical carcinogenesis. These viruses dysregulate the cell cycle and tumor suppressor genes (TP53 and pRb) through overexpression of viral early genes E6 and E7. Certain HPV strains (HPV serotypes 16, 18, 45, and 56) are classified as high-risk types, because they are associated with a majority of cases. HPV types 30, 31, 33, 35, 39, 51, 52, 58, and 66 are classified as intermediate oncogenic risk. In addition to viral infection, chronic cigarette smoking, multiple sexual partners, and immunosuppression increase the risk of cervical cancer14,15 (see Figure 26-6).

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FIGURE 26-6 A, Biopsy specimen revealing cancerous epithelium of the uterine cervix (hematoxylin and eosin stain). B, Human papillomavirus DNA detected in cervical epithelium by in situ hybridization.

(Courtesy Dr. Michael Cibull, Lexington, Kentucky.)

Cervical cancer typically has a long asymptomatic period before the disease becomes clinically evident. The cancer classically manifests in women who are between 40 and 60 years of age. The earliest preinvasive changes are diagnosed by Pap smear. Further evaluation is made by colposcopy and colposcopy-directed biopsy. If neoplastic cells penetrate the underlying basement membrane of the uterine cervix, widespread dissemination can occur. Metastases often affect renal tissues, resulting in ureteral obstruction and azotemia. Treatment is based on the stage of the disease and involves hysterectomy in the early stages and radiation therapy for disease that extends to or invades local organs. The 5-year survival rate is relatively high (see Table 26-1) but drops below 50% when the cancer extends to and beyond the pelvic wall.15

The ACS recommends that a Pap smear and professional pelvic examination be performed in women at the onset of sexually activity or at 18 years of age. Because cervical cancer is associated with immunosuppression, the Centers for Disease Control and Prevention (CDC) advises all women who are seropositive for human immunodeficiency virus (HIV) to receive semiannual screening beginning the first year after diagnosis. Health care providers may elect to screen less often when three annual examinations in a row are negative.16

Colorectal Cancer

Cancer of the large bowel (colon and rectum) is the most common malignancy of the gastrointestinal tract and overall the fourth most common cancer of persons living in the United States. This cancer was diagnosed in approximately 160,000 persons in the United States in 2010, and nearly 60,000 people died of the disease in that year.8 Colorectal cancer accounts for about 10% of all cancers in the United States and carries a 5-year survival rate of 61%. Over the past 2 decades, mortality has decreased for white women and men but increased in African American men and women.8,17

The vast majority of colorectal cancers are adenocarcinomas (Figure 26-7). Inherited predisposition and environmental factors contribute to their development. Genetic abnormalities in chromosome 5 (in familial adenomatous polyposis), chromosome 17 (TP53 gene), and chromosome 18 (DCC gene) are contributory. An initiating and probably obligatory event is the oncogenic activation of the adhesion protein, beta-catenin, resulting from its overexpression, or loss of its negative regulator, the adenomatous polyposis cancer protein (APC). These abnormalities result in an upregulation in cell cycle signaling. Patients with chronic inflammation (ulcerative colitis) have approximately 10 to 20 times the risk of colorectal cancer as in the general population. The risk also increases with high-fat diet (40% of total calories), low dietary fiber intake, and smoking cigarettes for 20 years or more. By contrast, use of nonsteroidal antiinflammatory drugs (NSAIDs) and folate supplementation reduces the risk for colorectal cancer. Colonic adenomas (polyps) have malignant potential; however, less than 5% develop into carcinomas. The exception to this rule is in Gardner’s syndrome, in which virtually all affected patients develop malignant polyposis by age 40 unless treated.1820

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FIGURE 26-7 Destructive effects of colon cancer.

(From Klatt ED: Robbins and Cotran atlas of pathology, ed 2, Philadelphia, 2010, Saunders.)

Colorectal cancer often is not diagnosed until age 40 and increases in incidence after age 50. Risk rises sharply by age 60 and doubles every decade until it peaks at age 75 years. Spread is by direct extension through the bowel wall and invasion of adjacent organs by lymphatics and the portal vein to the liver. The major signs and symptoms of colorectal cancer are rectal bleeding, abdominal pain, and change in bowel habits (constipation). Presenting symptoms may include those referable to invasion of adjacent organs (kidney, liver, vagina).1820 Screening for colorectal cancer as recommended by the ACS is summarized in Box 26-4 and also Table 26-3.

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Box 26-4

American Cancer Society (ACS) Colorectal Cancer Screening Guidelines

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Colonoscopy is the preferred approach for evaluating a patient for colorectal cancer. This approach permits tissue and brush biopsy to be performed. Staging of the patient is aided by endoscopic ultrasonography and computed tomography (CT) scanning. Surgical excision is the treatment of choice with lesions encroaching the distal 5 cm of the colon, resulting in colostomy. Radiation therapy is used for treatment of rectal and anal cancer. Chemotherapy (fluorouracil and leucovorin for up to 6 months or, more recently, topoisomerase I inhibitors [camptothecins] and oxaliplatin) are used when metastatic spread occurs. Liver metastases have been treated with hepatic arterial therapy using implantable pumps and injection ports to deliver chemotherapeutic agents.1820

The poor prognosis with advanced colorectal cancer (stage III or IV) emphasizes the need for annual screening of at-risk adults. Digital rectal examination, fecal occult blood test, stool DNA testing, sigmoidoscopy, colonoscopy, and barium enema with air contrast are the screening procedures for colorectal cancer. The ACS recommends that screening start at age 50 for both men and women and even earlier if a family history exists, especially among first-degree relatives of colorectal cancer, preexisting inflammatory bowel disease, a personal history of colorectal cancer or adenomatous polyp, or a family history of hereditary colorectal cancer syndromes (e.g., familial adenomatous polyposis, Peutz-Jeghers syndrome, Gardner’s syndrome). Digital rectal examination and a test for occult blood should be performed once a year. Sigmoidoscopy is recommended every 5 years and colonoscopy every 10 years. A barium enema can be performed in place of the sigmoidoscopy and colonoscopy.21

Lung Cancer

Lung cancer is the cause of 14% of cancer cases and is the leading cause of cancer deaths (almost 157,000 deaths annually) in the United States (see Table 26-1).8 Although it maintains a similar incidence with breast and prostate cancer, the number of deaths caused by lung cancer exceeds the two combined. The number of new cases has been declining in men since 1984; by contrast, the incidence in women increased in the 1980s and 1990s and only recently declined. Lung cancer is more prevalent in industrialized countries, but increased incidence in nonindustrialized countries has resulted from the introduction of cigarettes into these regions. Overall, more than 85% of cases are related to smoking tobacco with a dose-dependent effect. In 60% of human lung cancers, the p53 tumor suppressor gene is mutated. Current evidence suggests that polycyclic aromatic hydrocarbons (e.g., benzopyrene metabolite) of tobacco smoke form adducts within the TP53 gene that contribute to an abnormally functioning p53. Deletions in chromosomal 3p and 9p and overexpression of the ras and myc oncogenes and growth factor receptor c-erbB-2 appear to be important steps in malignant transformation. Risk of lung cancer increases in persons who are exposed to certain inorganic minerals (asbestos and crystalline silica), metals (arsenic, chromium, and nickel), and ionizing radiation (e.g., radon).7

Histologically, lung cancers are divided into two groups. About 80% are non–small cell lung cancers (large cell undifferentiated 10%; squamous cell carcinoma [SCC] 30%; and adenocarcinoma 40%) (Figure 26-8), and 20% are small cell lung cancers (i.e., oat cell carcinoma). Small cell cancers have a rapid growth rate and metastasize early.22

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FIGURE 26-8 Large cell undifferentiated carcinoma infiltrating the entire lung shown in cross section.

(From Klatt ED: Robbins and Cotran atlas of pathology, ed 2, Philadelphia, 2010, Saunders.)

Lung cancer is a clinically silent disease until late in its course. Tumors that grow locally can produce a cough or change the nature of a chronic cough or manifest as dyspnea on exertion. Cancers that invade adjacent structures can produce chest pain and dyspnea, hemoptysis or produce syndromes (e.g., Horner’s syndrome) from disruption of nerves in the chest and neck or endocrine, cutaneous, or neurologic manifestations. Metastases to the brain, bone, adrenal gland, and liver produce features associated with malfunction of these organs and lymphadenopathy. With advanced disease, patients present with anorexia, weight loss, weakness, and profound fatigue.22

Unfortunately, so far there is not any lung cancer screening test that has been shown to prevent people from dying of this disease. The use of chest x-ray imaging and sputum cytology (evaluating phlegm microscopically for abnormal cells) has been studied for several years. The recently updated studies have not yet yielded any value in screening programs for the early detection of lung cancer. Lung cancer screening is not recommended even for persons at high risk such as smokers.

The diagnosis of lung cancer is made by imaging studies, bronchoscopy, bronchial washings, brush and tissue biopsies, and histologic examination of the cells and tissue. Stage I and stage II non–small cell lung cancers are treated by surgical resection. Radiotherapy is used for more advanced non–small cell lung cancers and when patients with stage I or II disease refuse or are medically unfit for surgery. Chemotherapy using two or three agents (e.g., cisplatin, carboplatin, etoposide, vinblastine, vindesine) is employed in combination with radiotherapy for stage III and stage IV non–small cell lung cancers. Chemotherapy is the mainstay of treatment for small cell lung cancer. Adjuvant radiotherapy is used in patients with limited disease. Stage I lung cancer and stage II squamous cell lung cancers are associated with 5-year survival rates of more than 50%. The current 5-year survival rate for all stages of lung cancer is just 15.8%.23 Despite the poor prognosis, national recommendations have not been made in the United States to deploy diagnostic image screening for the detection of lung cancer even in high-risk persons.22

Prostate Cancer

Prostate cancer is the second most common cancer (approximately 234,000 cases per year) and the most common cancer of men in the United States (see Table 26-1). It is the second leading cause of cancer deaths among men (nearly 28,000 per year).8 Prostate cancer develops in approximately 9% of white men and in 11% of African American men. Family history and race (African American) are definitive risk factors for the development of this disease.24

At present, the etiologic factors for prostate cancer remain unknown. High dietary fat intake and mutations in chromosome 1 (1q24-25) and X (Xq27-28) appear to increase the risk for prostate cancer. Overexpression of the c-myc oncogene also is commonly detected in solid tumors such as prostate cancer.24

More than 90% of all prostate carcinomas are adenocarcinomas. They typically arise at multiple locations within the gland. Cancer of the prostate produces few signs and symptoms other than problems in urination (hesitancy, decreased force of urination) that, if present, occur late in the course of the disease. Thus screening procedures are paramount to the successful management of this disease. Methods used to screen for prostate cancer include the digital rectal examination (DRE) in combination with blood tests for prostate-specific antigen (PSA), and endorectal ultrasound imaging (Box 26-5; see also Table 26-3). The PSA velocity (change in the PSA level over time) aid in the diagnosis. The upper normal level for the PSA is 4 ng/mL. Transrectal ultrasound–guided needle biopsy is recommended for patients with the following findings24:

PSA value greater than 10 ng/mL

A positive DRE (palpable nodule or abnormality); even if the PSA value is less than 4 ng/mL, a positive DRE represents about 25% of all prostate cancer

PSA value between 4 and 10 ng/mL, a negative DRE

PSA value less than 4 ng/mL, a negative DRE, and a PSA value that has increased from 1 year to the next by 0.75 ng/mL (PSA velocity) or more

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Box 26-5

American Cancer Society Recommendations for the Early Detection of Prostate Cancer

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Radionuclide scanning or pelvic magnetic resonance imaging (MRI) is recommended for men diagnosed with prostate cancer with a PSA greater than 10 ng/mL to determine the extent of the disease. Metastasis occurs by lymphatic or hematogenous d/>

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Jan 4, 2015 | Posted by in General Dentistry | Comments Off on 26: Cancer and Oral Care of the Cancer Patient
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