Cancer

Diane M Opatt, MD, Clinical Instructor of Surgery, Temple University School of Medicine; Assistant Program Director, Department of Surgery, Abington Memorial Hospital
Christina Chung, MD, Staff Physician, Department of General Surgery, Tulane University Health Sciences Center; Mary Jo Wright, MD, Associate Professor of Surgery, Chief of Breast Surgery Service, Tulane University School of Medicine; Medical Director, Breast Cancer Center, Medical Center of Louisiana, New Orleans; Krzysztof Moroz, MD, Program Director, Associate Professor, Departments of Pathology and Laboratory Medicine, Tulane University Health Sciences Center; R Edward Newsome, MD, Program Director and Chief of Plastic Surgery, Henderson Chair in Surgery, Assistant Dean for Graduate Medical Education, Tulane University School of Medicine




Introduction

History of the Procedure

Over the greater part of the last century, all forms of breast cancer have been treated by aggressive surgical resection. In 1894, Halsted described the procedure of en bloc removal of all breast tissue, draining lymph nodes and pectoralis muscles for the treatment of breast cancer. This technique of radical mastectomy became the standard of care for decades based on an understanding that cancer growth proceeded in stepwise fashion via the lymphatics, thus could be controlled with surgical excision.

In 1971, Fisher et al challenged this standard and demonstrated in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-04 trial that radical mastectomy had no survival benefit over mastectomy with radiation or mastectomy with delayed axillary dissection. In a subsequent study, NSABP B-06, patients were randomized to total mastectomy versus lumpectomy and radiation therapy (XRT), and no survival benefit of total mastectomy was found. However, benefit was observed in the decreased rate of local recurrence in women receiving XRT. Development of new chemotherapeutic and hormonal agents has further revolutionized the management of breast cancer.

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center, Women's Health Center, and Imaging Center. Also, see eMedicine's patient education articles Breast Cancer, Mastectomy, Breast Lumps and Pain, Breast Self-Exam, and Mammogram.



Problem

Worldwide, the overall incidence of breast cancer varies markedly but appears to be rising. Far eastern countries such as Japan, which historically have enjoyed low rates in comparison to the United States, are seeing a rapid rise in incidence. Although the United States has the highest reported incidence of breast cancer in the world, several western European nations such as Iceland, Italy, France, Sweden, and the United Kingdom trail closely behind. Incidence has been historically lower in Eastern Europe, the Middle East, and the Far East, but countries such as Japan and Singapore have seen a 2-fold rise over the past few decades.

Frequency

Of American women, 13% will be diagnosed with breast cancer in their lifetimes, making it the most common nonskin cancer among women. In addition, more than 3% will die from the disease. Breast cancer has surpassed lung cancer as the leading cause of cancer death in women worldwide, accounting for more than 400,000 deaths per year. In the United States, breast cancer trails only lung cancer as the second most common cause of cancer death in women. In 2002, more than 1.15 million new cases were diagnosed worldwide. More than 200,000 of these were in the United States alone.

The 1980s saw the greatest rise in incidence, which may have been due to a combination of improvements in screening techniques, data collection, and treatment modalities. Despite this surge in newly-diagnosed cases, mortality rates have been declining over the last decade. The decline is widely attributed to earlier detection via screening mammography and improvements in hormonal therapy and chemotherapy.


Etiology

Risk factors for the development of invasive breast cancer include female gender, age, family history, age at the time of first parturition, personal history of previous breast cancer, hormone replacement therapy, history of atypical hyperplasia or noninvasive lesions, and genetics.

* Female gender: The incidence of breast cancer in women exceeds that in men by 100:1. Overall, 1 of every 8 American women develops breast cancer in her lifetime.
* Age: In American women, risk increases from 1:5900 to 1:290 between the third and eighth decades. A woman aged 60-79 years has a 1:14 chance of developing invasive breast cancer, compared with a woman younger than 39 years, who has a 1:225 probability.
* Age at birth of first child: If aged 30 years or older, relative risk is 2 times that of patients who gave birth when younger than 20 years.
* Personal history of breast cancer: This also is a recognized risk factor. This factor depends on patient age at time of diagnosis. Risk is increased for younger women.
* Noninvasive carcinoma (ductal carcinoma in situ [DCIS]/lobular carcinoma in situ [LCIS]) on previous biopsy: This also is a marker for development of invasive lesions.
* Benign proliferative changes with atypical hyperplasia: These may increase relative risk by 4 times. Atypical hyperplasia may be observed in as many as 10% of specimens from biopsy.
* Early menarche and late menopause: These also are associated weakly with increased relative risk of breast cancer.
* Menopausal hormone replacement therapy: Multiple studies, including the Women's Health Initiative and the Million Women Study in the United Kingdom, have shown an increased risk of breast cancer in postmenopausal women who are either recent or current users of estrogen alone or in combination with progestin. In addition, the combination use of estrogen with progestin has been associated with an even greater risk of breast cancer, particularly of lobular carcinoma. Increased risk is also related to increased duration of use; this risk can be reduced over time, following the termination of hormone replacement therapy.
* Family history: Degree of relativity of the family member with breast cancer affects individual risk. For example, the relative risk of patients with an affected first-degree relative is 1.5-2 times higher when compared to controls without affected family members. Even more significantly, having two first-degree relatives affected (female or male) increases relative risk by more than 4-6 times when compared to patients without this risk factor. Third, age of the affected relative at time of diagnosis also influences risk. A patient with a mother diagnosed when younger than 60 years is at 2 times increased risk. Finally, bilateral cancer in a first-degree relative may increase risk by more than 6 times.