Paget's disease of the breast

Staff Development Special

Follow this guide to lead a staff discussion on breast cancer.

As diagnostic technology options increase, so do survival rates. Review the latest regarding disease detection and treatment to best meet patient needs.

Staff development CE:

As diagnostic technology options increase, so do survival rates. Review the latest regading disease detection and treatment to best meet patient needs.

By Carolyn Weaver, RN, MSN, AOCN

Abstract: Explore innovative breast cancer initiatives, including ductal lavage, digital mammography, sentinel lymph node biopsy, chemoprevention, radiation therapy, hormonal therapies, and targeted therapies.

[Nurse Manage 2002:33(11):27-34]

Breast cancer is the second leading cause of cancer death among U.S. women

An estimated 203,500 women and 1,500 men in the United States will learn that they have this disease in 2002.1 The overall lifetime risk for American women is 1:8, which essentially means that out of 8 females born today, 1 will receive a breast cancer diagnosis in her lifetime.2

During the past several decades, experts have detected more breast cancers because women live longer and receive regular mammography screening. Technologic advances allow for quicker detection and treatment of more early-stage cancers, boosting patients' long-term survival rate to almost 86%.3

Innovations regarding adverse reaction management have also improved cancer patients' quality of life, helping to minimize nausea and fatigue. And although some breast cancer, namely metastatic, remains incurable, advances in systemic therapies-including new oral agents, hormonal therapies, and drug combinations-prolong survival.

Disease background

Two major categories of breast cancer exist: noninvasive and invasive. Noninvasive, or in situ, breast cancers are those that haven't extended beyond their duct or lobule of origin into the surrounding breast tissue. Conversely, invasive, or infiltrating, breast cancers have extended into the surrounding breast tissue and have the potential to metastasize. Unfortunately, most breast cancers are this type. Researchers believe that most invasive cancers probably originate as noninvasive.

Lobular carcinoma in situ (LCIS) is considered a risk factor for invasive cancer; approximately 20% to 30% of those with LCIS develop an invasive breast cancer in the 25 years following initial LCIS diagnosis. Ductal carcinoma in situ (DCIS), by definition, doesn't spread beyond the breast. The prognosis for DCIS is excellent, with a cure rate close to 100%.

The most common type of invasive breast cancer is ductal, which originates in the milk ducts and accounts for 79% of all breast cancers. Lobular breast cancer, which originates in the lobules, is the second most common type of invasive breast cancer, accounting for approximately 10% of all breast cancers. Invasive lobular cancer has a slightly higher chance than ductal cancer of developing in the opposite breast.

The prognosis for stage I and II ductal and lobular cancers is close to 95% survival at 5 years. Other less common types, most of which originate in the ducts, include tubular, medullary, and mucinous (colloid). Paget's disease, a rare type of breast cancer, originates in the nipple. Prognosis for these less common types is usually very good. (See "Where breast cancer gets its start.")

Prognostic factors that influence survival and guide the patient's treatment plan include:

* whether the tumor is noninvasive or invasive

* the tumor's size, hormone receptor status, grade (how fast it's growing and how different it looks from normal cells), and its HER2 status-a protein that when overexpressed, may indicate a more aggressive cancer

* whether the tumor is confined to one area of the breast

* if there's any spread to the axillary lymph nodes

* the patient's menopausal status, age, and other medical conditions.

Risk factors

What are the biggest risk factors for breast cancer? Two uncontrollable elements-female gender and advanced age. Numerous other factors that increase risk relate to exposure to hormones, specifically estrogen. These include early age at first menses, late menopause, first pregnancy after age 29, and having never given birth.

Additional factors that may increase a woman's risk for breast cancer include:

* use of hormone replacement therapy

* receipt of ionizing radiation

* physical inactivity

* a high-fat, high-calorie diet

* excessive alcohol consumption.

The association of weight and breast cancer risk depends on menopausal status. For postmenopausal women, being overweight increases the risk for breast cancer and the risk of its recurrence. In premenopausal women, the opposite seems true: the thinner the woman, the higher the risk.

As with all cancers, breast cancers are genetic, resulting from a mutation in a gene that promotes abnormal cell growth. Researchers have identified two genes that every human possesses, BRCAI and BRCA2, which when mutated, increase an individual's risk of developing breast cancer.

A family history of breast cancer, specifically in a first-degree relative such as a mother, sister, or daughter, can also increase an individual's risk. Refer women with family histories of breast cancer, particularly those anxious about their own risk, to a breast cancer risk assessment program. This will allow them to get a better understanding of their relative risk and give them the opportunity to learn about methods of risk reduction and early detection. Surprisingly, familial cancers only account for 10% to 20% of all breast cancers.

Recent studies suggest that changes in milk duct cells may indicate an increased breast cancer risk. Ductal lavage is a relatively new method of obtaining a sample of ductal cells for risk analysis. In this process, health care professionals obtain fluid through ductal massage and nipple aspiration. The procedure specifically involves injecting saline through a cannula via the nipple to rinse the ducts and collect a sample of cells in the return fluid. Finding the presence of atypical cells can assist in assessment of risk-reduction and treatment options. It can also help determine which high-risk patients may require closer, more active management. Ductal lavage requires intensive training; its long-term utility in highrisk individuals remains undetermined.

Another breast cancer risk factor is the presence of atypical hyperplasia (presence of numerous abnormal cells that aren't yet cancer) in the ducts or lobules, as determined by biopsy, which may increase an individual's breast cancer risk fourfold.

Some high-risk women choose prophylactic mastectomy. While prophylactic mastectomies don't prevent breast cancer entirely because some of the breast tissue is left on the chest wall, the procedure reduces cancer risk by approximately 90%.

Detection

Established by the National Cancer Institute and the American Cancer Society, screening guidelines for asymptomatic women of average risk include a mammogram every year for women age 40 and over (younger in women identified as high risk), yearly clinical breast exams, and monthly breast self-exams. (See "How and when to screen.")

Breast cancer signs and symptoms may include the presence of a lump or thickening in the breast, a dimpling or puckering of the skin, spontaneous nipple discharge, a change in the size or shape of the breast or in the direction the nipple points, or an abnormality that's not felt, but is detected by one of the following methods:

* Traditional mammography. The gold standard in breast cancer detection, mammograms can detect a breast cancer 5 mm in diameter, whereas humans often can't feel the lump until it's about 1.0 cm. Mammograms can also detect DCIS. Fortunately, many breast cancers are detected when they're very small, resulting in a high cure rate.

Mammograms aren't perfect, however, failing to detect cancers approximately 10% to 15% of the time. And their value is limited in younger women, who are more likely to have dense breasts, making visualization difficult.

* Digital mammography and computerassisted diagnosis (CAD). Derivatives of traditional mammography, digital mammography and CAD can improve visualization by allowing for changes in image contrast and magnification, making it easier to transmit images to other facilities. Ongoing studies evaluate if this form of mammography is superior to traditional mammography in terms of ability to detect a breast cancer.

* Ultrasounds. These tests can distinguish between normal and abnormal breast tissue. This method typically distinguishes fluid-filled lesions from solid ones, and is often used in younger women with a palpable lesion.

* Magnetic resonance imaging (MRI). A patient may undergo an MRI if she has very dense breasts or inconclusive mammograms.

Positron emission tomography (PET) scan. A relatively new imaging test for breast cancer, a PET scan not only finds masses that may be cancer, but determines whether cancerous masses are active and growing or inactive and shrinking. In 2002, Medicare agreed to cover the cost of PET scans for women with advanced or recurrent breast cancer.

* Thermo-scans. These monitor changes in temperature as a detection method. Researchers continue to investigate their effectiveness.

* Biopsy. Patients undergo a biopsy to determine a definitive diagnosis or whether a lump is a cyst, a noncancerous tumor, or a cancerous lesion. Biopsy types include fine-needle aspiration, core-needle, stereotactic, needle localization, excisional, or incisional.

Caregivers perform fine-needle aspiration and core-needle biopsies on a palpable mass with a local anesthetic. Stereotactic biopsy involves using a special device on the mammography machine that pinpoints exactly the area inside the breast to be biopsied. A needle localization biopsy uses radiographic assistance to locate a nonpalpable mass. An excisional biopsy requires surgery, during which surgeons remove the entire abnormality-- not just a portion-for pathological analysis. An incisional biopsy, on the other hand, entails the removal of a small piece of tissue for sectioning and examination. Both are normally outpatient procedures requiring local anesthesia.

Treatment options

Generally, breast cancer treatment falls into two categories: local and systemic. Local treatments amenable to breast cancer are surgery and radiation therapy Effective systemic treatments include chemotherapy, hormonal therapy, and targeted therapy.

Caregivers recommend treatment plans based on multiple factors, primarily, whether the cancer is invasive or noninvasive, the tumor's size and grade, the number of cancerous axillary lymph nodes, the patient's hormone receptor status, and the ability to obtain clear surgical margins.

Local treatments

* Lumpectomy: For breast cancer patients, a lumpectomy involves removing the cancerous lump and a surrounding area of healthy tissue around the tumor's margins. The term clear margins indicates that the procedure has attained the desired margin size around the lump. There's no standard agreement on what constitutes desired margin size: The size of a dear margin differs among institutions and could be anywhere from a 2- to 5-mm margin to the site of the lumpectomy incision.

* Simple mastectomy: This involves removal of the breast only and may be done in cases when lymph node status isn't needed (a noninvasive cancer) or when lymph node status is already known from a previous lumpectomy and ancillary lymph node sampling, but clear margins couldn't be obtained, necessitating a mastectomy. If the patient has noninvasive cancer (DCIS), surgeons may recommend a simple mastectomy, primarily because DCIS often isn't confined to a small area of the breast.

* Modified radical mastectomy: Patients with invasive breast cancer may require this type of mastectomy, which is removal of the breast and the axillary lymph nodes.

Six modern prospective randomized clinical trials comparing breast conservation therapy (lumpectomy and radiation therapy) and mastectomy showed equivalence in terms of survival in women with early stage breast cancers 4

* Lymph node removal: Because the number of cancerous lymph nodes guides further treatments, the purpose of removing axillary lymph nodes in patients with invasive breast cancer is diagnostic, and in the event of positive lymph nodes, it's therapeutic. Traditionally, surgeons perform a standard axillary lymph node dissection for invasive breast cancer, resulting in the removal of level I and level II lymph nodes.

* Sentinel lymph node biopsy: In recent years, sentinel lymph node biopsy emerged as a leading advancement in breast cancer management, helping to determine appropriate surgical management for the patient. Based on the theory that if cancer spreads through the lymphatic system, it will first appear in the lymph node closest to the tumor, this technique involves the injection of dye and/or a radioisotope into the periareolar area or in the vicinity of the tumor either before tumor removal or in the primary tumor bed after it's removed. These injections allow for identification of sentinel lymph nodes in the axilla and/or in the internal mammary node chains in more than 95% of cases.

Surgeons inject the radioisotope adjacent to the tumor preoperatively and then conduct a lymphoscintigraphic scan several hours later. Once in the operating room, they inject the blue dye into the adjacent area and look for affected nodes. They may also use a gamma probe to identify affected lymph nodes. Pathologists receive these nodes during the surgery to conduct a frozen section review.

If the frozen section is positive for malignant cells, then surgeons perform a standard axillary lymph node dissection at that time. If it's negative, surgeons don't remove additional lymph nodes and the pathologists extensively dissect the node. If the final pathology, which may take 3 to 5 days to complete, indicates lymph node metastasis, then the patient will require a standard axillary lymph node dissection.

The National Comprehensive Cancer Network has upgraded sentinel lymph node biopsy to a treatment option equal to axillary node dissection if patients meet the criteria and there's an experienced surgical team available.

Failed sentinel lymph node localization occurs more often in tumors in the inner half of the breast, lobular carcinomas, and those with a high body mass index. Researchers continue to explore other predictive factors of lymph node involvement, such as tumor size, age, or lymphovascular invasion.

* Radiation therapy: Standard treatment involves administering external beam radiation 5 days a week for approximately 6 weeks. The patient's entire breast receives radiation for about 5 weeks; during the last week, the patient receives a boost of radiation to the site where the original tumor resided. Common side effects include redness, dryness, peeling skin, and fatigue. Less common side effects include rib fractures, cardiovascular effects, and leukemia.

Patients undergo radiation in conjunction with a lumpectomy for early stage breast cancer. They may also receive it after a mastectomy when the tumor size is greater than 4 cm, if surgeons couldn't obtain a clear or negative deep margin, or with the presence of more than 4 cancer-positive lymph nodes. Even in very small breast cancers with dear margins, there's a 5% to 6% risk of local recurrence after a lumpectomy without irradiation.

Current clinical studies are examining the role of radiation after mastectomy in women with 1 to 3 positive nodes.

An alternative to traditional radiation therapy 4- to 5-day brachytherapy delivers radiation after surgery through catheters placed at least 2 cm behind the tumor bed in all directions. Some experts favor this technique because it delivers radiation in a shorter time frame to specific sections of the breast, thus minimizing patient complication.

Other alternatives to traditional radation therapy include a portable electron beam driven-device to deliver radiation in 20 to 30 minutes in an operating room, intraoperative radiation, and three-dimensional radiation, especially in women with large breast volume and with uncharacteristic tumor bed locations.

Systemic treatments

* Chemotherapy: Advances in breast cancer research have resulted in recommendations for more women to get chemotherapy after their surgery, which is referred to as adjuvant chemotherapy. Studies demonstrate that adjuvant systemic therapy such as chemotherapy or hormonal therapy decreases breast cancer recurrence and prolongs disease-free survival in women with tumors greater than 1 cm in size, regardless of their lymph node status. This is a change from past years when specialists only recommended adjuvant chemotherapy for women with cancerous lymph nodes.

While chemotherapy regimens differ among facilities, two standard U.S. outpatient regimens for node-negative breast cancer exist-Regimen #1: doxorubicin (Adriamycin) or epirubicin (Ellence) and cyclophosphamide (Cytoxan) given on a schedule of once every 21 days for 3 months; regimen #2: cyclophosphamide, methotrexate, and 5-fluorouracil (Fluorouracil) given on day 1 and 8 for 6 months. When surgeons find positive lymph nodes, the initial regimen may be followed by 4 cycles of paclitaxel (Taxol) or another taxane for additional benefit.

Given before surgery, neo-adjuvant chemotherapy may decrease the tumor's size, resulting in the opportunity for breast conservation surgery. Patients may also receive it to decrease further spread of locally advanced cancer at diagnosis.

* Hormonal therapy: An emerging field in breast cancer treatment, hormonal therapies are usually recommended in women with estrogen or progesterone receptor positive breast cancers.

Hormone receptor positivity suggests that the hormone promotes the growth of the cancer. Two-thirds of breast cancer is hormone receptor positive. In the adjuvant setting, hormonal therapy's main goals are to prevent a recurrence of a diagnosed cancer or development of a new breast cancer. In the case of metastatic disease, the goal may be palliation or prolonged survival with stable disease.

Oncologists often prescribe selective estrogen receptor modulators (SERM), such as tamoxifen (Nolvadex). Patients take SERM orally for 5 years to prevent estrogen from binding to the breast cells' estrogen receptors. Studies find that in the adjuvant setting, SERM decreases the patient's risk of developing another breast cancer by 45% to 50%; however, they increase risk for blood dot formation and other adverse effects such as endometrial cancer.

Another class of hormonal agents, known as aromatase inhibitors (Als), stands out as an effective therapy option. AIs work by inhibiting the conversion of androgens to estrogens. In the past, patients who took these medications had progressed on other b/b antistrogen therapies, such as tamoxifen. In light of current research results, oncologists may recommend an AI before SERM for postmenopausal estrogen receptor positive women with metastatic disease. AIs include letrozole (Femara), exemestane (Aromasin), and anastrozole (Arimidex), all of which patients take orally.5

Early results of a randomized clinical trial published in December 2001 that compared anastrozole, tamoxifen, and a combination of both showed that anastrozole, alone, was the most effective treatment in preventing women with early stage breast cancer from developing a future breast cancer. Researchers also found that anastrozole is less likely to cause endometrial cancer or blood clots. Most oncologists, however, view this result with caution due to a lack of long-term data. While most medical oncologists continue to prescribe tamoxifen in the adjuvant setting, they may recommend anastrozole to women with a history of blood clots.6

Fulvestrant (Faslodex) gained approval in April 2002 for the treatment of estrogen receptor positive metastatic breast cancer in postmenopausal women whose disease had progressed despite antiestrogen hormonal therapy, such as tamoxifen. Acting as a pure antiestrogen, fulvestrant binds, blocks, and degrades estrogen receptors permanently.

Fulvestrant is less likely to cause hot flashes and endometrial cancer than tamoxifen. Patients receive it as a monthly intramuscular injection.7

* Targeted therapies: While traditional therapies may effectively eradicate cancer cells, they also, unfortunately, impact normal cells. Not so with targeted therapies.

All cells produce a protein called HER2, which one-fourth of breast cancers over-express. This protein causes cancer cells to grow rapidly. Trastuzumab (Herceptin), the most widely known targeted therapy for metastatic breast cancer, is an antibody that reacts against the FIM protein on the surface of the tumor cells. Compared to standard chemotherapy, trastuzumah offers a greater ability to target cancer cells and spare normal cells. It's associated with relatively mild side effects in most women.

Advances in molecular biology continue to target cellular signaling mechanisms, including the epidermal growth factor receptor (EGFR). Believed to play a role in tumorigenesis, EGFR is expressed at high levels in many cancers. Clinical data suggest that excessive levels of the protein are linked to poor prognosis, including tumor invasion and metastatic cancer development. Researchers continue to define the clinical value of determining the status of EGFR.

Anti-angiogenesis therapy: A drug called bevacizumab (Avastin) halts the growth of new blood vessels, thus starving the tumor of the nutrients it needs to survive. Patients receive this medication in limited clinical trials.

* Cytotoxic therapies: Pemetrexed (Alimta) shows promising activity in those who've failed prior cytotoxic therapies. Its toxicities are manageable. Also, researchers are examining a new class of microtubule-targeted therapeutics called epothilones.

Advocate a sound approach

The sheer number of ongoing breast cancer research challenges even the most astute caregiver. Although staying apprised of ever-evolving advances can prove overwhelming, you'll want to remain as knowledgeable as possible to offer patients insight and support regarding prevention, detection, and treatment. Carefully review the latest in nontraditional therapies, the availability of clinical trials, and the current care standards to ensure that you're able to help those in your care decipher their best treatment options.

References

1. Jemal, A. et al.: "Cancer Statistics, 2002," CA: A Cancer Journal for Clinicians. 52(l):23-47, Jan.-Feb., 2002.

2. National Cancer Institute: Lifetime Probability of Breast Cancer in American Women. Available on-line: http://www.nci.nih.gov. Last updated September 13, 2002.

3. Harris, J., et al.: Diseases of the Breast, 2nd edition. Lippincott Williams & Wilkins: Philadelphia, Pa., 2000.

4. Ibid.

5. Dow, K.: "Existing and Emerging Endocrine Therapies for Breast Cancer," Cancer Nursing. 25(2S):6-11, 2002.

6. National Comprehensive Cancer Network and the American Cancer Society: Breast Cancer Treatment Guidelines for Patients, version IV, 2002.

7. Dow, K.: loc cit.

About the author

Carolyn Weaver is a Clinical Nurse Specialist and Patient Education Coordinator at Fox Chase Cancer Center, Philadelphia, Pa.

Copyright Springhouse Corporation Nov 2002
Provided by ProQuest Information and Learning Company. All rights Reserved