INTRODUCTION
While the epidemic of obesity in this country has well-known detrimental effects on the cardiovascular system and increased problems with arthritis and diabetes, its effect on the female breast has only more recently been realized. This chapter reviews the effects that obesity has on benign breast problems, breast imaging, and breast cancer management. A better understanding of the overall negative impact that obesity has especially on cancer prognosis, recurrence, and treatment will allow the practicing gynecologist to have a more frank discussion about the importance of maintaining a healthy body mass index (BMI).
BENIGN DISEASE
A variety of common skin conditions manifest on the breast, in the inframammary folds, and in the axilla and are exacerbated by obesity. Obesity results in numerous changes to skin, including increased sweat gland function, changes in microcirculation, and additional shearing forces in dependent areas.1
Intertrigo, erythematous skin plaques that develop in the inframammary skinfolds, is due to increased friction and moisture that leads to skin damage. Yeast, most commonly Candida albicans, often exists in these regions and requires treatment with topical antifungal powders. Some patients may require oral fluconazole for resistant cases.2
Other skin infections commonly seen in the obese patient include folliculitis, cellulitis, and even necrotizing soft tissue infections. The breast can be a site of these infections, especially in areas where increased skin friction leads to skin damage and susceptibility to infection. A recent study by Eggerstedt et al. examined all types and locations of necrotizing soft tissue infections; obesity and diabetes were commonly found. The mortality rate for superobese (BMI > 50) patients was 50% in this small study.3 It is important to closely monitor and evaluate breast infections in the obese population because these patients might be more vulnerable to more significant complications, especially when diabetes accompanies obesity.
Hidradenitis suppurativa is a disease that affects the apocrine glands and can be found in areas like the axilla, inframammary region, groin, and perineum. The disease is multifactorial and difficult to manage, but manifests as chronic abscesses and subcutaneous fistula tracts, which frequently drain and become infected.1 The disease seems to be more frequently seen in the obese population. Medical management includes topical and oral antibiotics, but these treatments often have limited efficacy. The most effective treatment is surgical excision of the affected tissue and either primary skin closure or sometimes skin grafting with widespread disease.
The breast parenchyma refers to all the functional breast tissue, including the glands and breast ducts, while the stroma is essentially the support structure to the breast, such as Cooper’s ligaments and the surrounding fatty tissue. A number of benign conditions affect the breast tissues; most are not associated with any increased risk for breast cancer. Some commonly seen benign breast diseases are discussed next, but there is limited published evidence that any of these “in-breast” conditions occur more often in the obese population, but instead are common in all patients.
Fat necrosis is a benign condition that occurs after breast trauma and is caused by inflammation of the adipose tissue. It can often feel like a dense mass and needs to be differentiated from cancer by imaging; occasionally, a biopsy is required. Epidermal inclusion cysts, “sebaceous cysts,” can be seen in the breast and are usually superficial, well-circumscribed lesions that are easily palpable. The cyst can become infected, and definitive treatment is excision of the cyst, including the cyst wall, to reduce the likelihood of recurrence. Breast cysts are common and can be easily distinguished from solid masses by breast ultrasound. Cysts are fluid filled and can be simple; when septations or irregular walls are present, cysts are considered complex and may require a core needle biopsy for diagnosis.4 Lipomas are benign, well-circumscribed, fatty tumors. On examination, these lesions feel soft and mobile and are not always easily seen on imaging. If there is uncertainty about the diagnosis, biopsy or surgical excision can be performed. Fibroadenomas are generally benign, well-circumscribed masses commonly seen in younger women (15–35 years old). These masses can grow slowly. Treatment includes observation for small lesions (<2 cm) and follow-up imaging to ensure stability or surgical excision for large or symptomatic lesions. A phyllode tumor is the more aggressive variant that cannot always be distinguished from a fibroadenoma until removed surgically. Therefore, a rapidly growing fibroadenoma should be removed because this may represent a phyllode tumor.
Bariatric surgery is one of the most common surgical procedures performed. On average, after gastric bypass surgery, patients lose about 60% of their body weight; for many patients, that can be greater than 100 pounds. With the marked reduction in breast adipose tissue, the fibroglandular portions of the breast become more obvious, and as a result the breast often feels more “lumpy” or dense and nodular. It is not uncommon for patients with new marked weight loss either to self-detect a new mass or to have a new mass detected on clinical breast exam. This frequently prompts immediate referral to a breast surgeon and diagnostic imaging with mammography or ultrasound. While imaging may note a change in the general appearance or density pattern, these new palpable masses are not true imaging abnormalities. These new masses should not necessarily be ignored. Clinicians should be aware of the possibility of a new breast mass in the patient with recent massive weight loss and treat the patient accordingly.
BREAST IMAGING
Screening mammography has clearly demonstrated a decrease in the risk of death from breast carcinoma.5 It has previously been suggested that obesity is associated with decreased compliance with routine screening mammography.6 The current national recommendations for screening mammography7 include mammography at least every 1–2 years beginning at about age 40. Obesity is associated with increased risk of postmenopausal breast cancer,8 as well as an independent prognostic factor for developing distant metastasis and dying.9 There are two questions to consider: (1) Is obesity perhaps associated with decreased compliance with routine recommended screening standards? (2) Is obesity associated with decreased sensitivity of mammography as a screening tool for breast cancer? Future research is needed to investigate these possible concerns. Both issues are discussed in the following sections.
In one of the largest population-based analyses performed, Bertz et al. examined specifically the association between BMI and compliance with routine recommended mammographic screening; the study used data from the 2004 Behavioral Risk Factor Surveillance System (BRFSS). Using weighted analysis of over 130,000 women aged 40 and over, the proportion of women who underwent screening mammography in the previous 2 years was stratified by BMI. Interestingly, these authors found that, after adjusting for numerous factors, including age, race, smoking status, general health perception, level of education, and income level, women who were underweight (BMI < 18.5) had lower odds of complying with regular screening mammography. Overweight and obese women (class I [BMI 30 to < 35] and II [BMI 35 to < 40]) showed significantly higher association with appropriate screening mammography utilization. Obese women in class III (BMI ≥ 40) trended toward underutilization, although the findings were not statistically significant.9 This study suggests that lack of compliance with screening recommendations does not explain the increased incidence of breast cancer in the obese population because there were no significant differences among the obese groups.
Yearly screening mammography is recommended for average-risk women starting at the age of 40, while women who are at a higher risk may benefit from mammographic screening at a younger age. Screening may continue until the patient would be unable to act on abnormal screening results due to age or comorbid conditions or when life expectancy is less than 5–7 years.10
Some barriers to screening that obese women may feel include disrespectful behavior, unwanted advice to lose weight, embarrassment about being weighed, negative attitudes of providers, as well as ill-fitting gowns and small equipment.11 Mammographic facilities may attempt to make obese women more comfortable by having sensitive personnel who are able to offer proper assistance. Waiting room chairs that are appropriate for women of all sizes as well as changing rooms and bathrooms with ample space may make the imaging experience more favorable and likely will increase compliance with screening.
In general, overweight women have less-dense breast tissue than normal-weight women on mammography, as well as larger breasts, which in turn leads to greater compression thickness.12,13 While less-dense breasts may decrease the masking effects of dense fibroglandular tissue and improve interpretation, the increased compression thickness of the breast in obese women leads to image quality degradation when technical factors such as geometric unsharpness and contrast are measured. Subtle or small lesions may be obscured, which may be a contributing factor to the observation that tumors found in obese women tend to be larger than those found in normal-weight women.13,14
With larger breasts, positioning the patient for quality mammography may be challenging, and multiple additional mammograms may be required, which makes proper hanging and reading of the images difficult. Obese women with large breasts may require multiple images in a tile or mosaic fashion to image the whole breast, especially in older units, which may have smaller detectors. Multiple mammograms in the craniocaudal position may be required to obtain images with both the nipple in profile and to image the posterior breast. Multiple mammograms in the mediolateral oblique position may be required to ensure that adequate compression is achieved both posteriorly and anteriorly (see Figure 11-1). Obese patients may have smaller breasts that wrap around laterally, which may require an additional exaggerated craniocaudal view to image lateral tissue. Imaging the inframammary fold may be difficult in an obese patient with large abdominal girth. In addition, breast folds may obscure portions of the breast in obese women with large breasts.15 The increased number of mammograms required to adequately image the entire breast as well as the increased breast thickness may result in increased radiation exposure in obese women.13
Evaluation of mammographic interpretation indicates obese women have higher rates of recall for additional views on screening mammogram when compared to normal-weight women, with increased rates of false-positive examinations.12,16 Overweight women were found to have increased rates of cancer detection, with tumors that were generally larger and at a more advanced stage.16
Digital breast tomosynthesis is a relatively new technology utilizing multiple low-dose acquisitions in an arc to create a cross-sectional image. Initial studies have demonstrated a decrease in recall rates, which is in part due to the ability to resolve summation artifact on cross-sectional images, as well as an increase in cancer detection due to an ability to negate some of the masking effect of dense fibroglandular tissue.17 Presumably, some of the same factors that affect obese women with standard mammography will have an impact on tomosynthesis, but further research is required (see Figure 11-2).
When a biopsy is required for calcifications or a lesion seen only on mammography, a stereotactic biopsy is recommended. Performing a stereotactic biopsy on obese patients may be challenging because of positioning, as many facilities use prone tables. Obese patients may have difficulty lying prone and staying still for the time required for a biopsy due to neck and back pain or difficulty breathing. In patients with a large abdomen, pulling the patient in far enough to access the posterior breast may be a challenge. Many prone tables also have a weight limit of 300 pounds.15 If a site that performs upright stereotactic biopsy cannot be found for patients ineligible for prone biopsy, the patient may need to undergo a needle-localized surgical biopsy for suspicious lesions.
Ultrasound of the breast may be performed for further characterization of lesions seen on mammography or on magnetic resonance imaging (MRI), in addition to evaluation of palpable masses. Screening ultrasound of the breast may also be used as an adjunct to mammography in women who are at high risk but unable to undergo MRI screening or in women with dense breasts.10,18 Ultrasound screening in patients with dense breasts has been shown to have a relatively low positive-predictive value, indicating a high number of additional tests performed for every additional cancer found that would not have been visible on mammogram, and the best use of screening ultrasound may require more research.18
Quality breast ultrasound begins with high-frequency transducer, typically a linear 12-MHz transducer. A linear 17-MHz transducer may be useful to evaluate small breasts that are less than 3 cm in thickness or to evaluate superficial masses.18 Deep lesions in a large breast may be difficult to visualize with high-frequency transducers, and a deep cyst may appear to be solid due to decreased resolution.15 Technologists who are experienced in breast ultrasound and careful correlation of the ultrasound findings with mammographic or MRI findings are also key to a quality examination.
In obese patients who may have larger, less-dense breasts, finding smaller masses that correlate to mammographic lesions may be difficult when the breast is quite mobile. Masses may be less difficult to visualize on ultrasound in less-dense breasts, as more echogenic fibroglandular tissue offers contrast to a hypoechoic or isoechoic mass.15
Ultrasound-guided biopsy is generally the preferred method of biopsy in most patients, as the patient is more comfortable in a supine position and real-time imaging of the biopsy device passing through the mass allows for fewer samples to be taken with a high level of confidence that quality samples were obtained. To keep the biopsy device parallel to the chest wall and minimize the risk of pneumothorax, a remote entry site may be required in obese women with large breasts and a deep lesion.15
Magnetic resonance imaging breast screening may be used in select patients with a greater than 20% lifetime risk of breast cancer by family history, those who are BRCA mutation carriers, and those with a history of chest irradiation, as well as for screening of the contralateral breast in a patient with newly diagnosed breast cancer.10 MRI may also be used as a problem-solving modality for evaluation of disease not fully assessed by mammogram and ultrasound.
Obese patients may be unable to obtain an MRI with table weight limits that range from 350 to 420 pounds, although newer tables accommodating patients weighing up to 550 pounds are available at some sites. Even though a patient may fall within the weight limit, they may be unable to obtain an MRI because of limitations on the gantry size, which has traditionally been 60 cm in diameter. Some units may offer up to a 70-cm diameter gantry size. The effective gantry size is diminished when a recommended dedicated breast coil is used.15
The use of radiopharmaceuticals with breast-specific gamma imaging (BSGI) or positron emission mammography (PEM) may be an adjunctive imaging modality in select patients,19,20 without some of the size limitations that MRI may impose. BSGI and PEM do use significantly higher levels of radiation than other modalities,21 and their availability is limited.
BREAST CANCER AND OBESITY
It is well known that obesity increases the risk of developing breast cancer, in particular estrogen receptor–positive disease, in postmenopausal women.22,23 Interestingly, for reasons that are unclear, obesity seems to be protective in premenopausal women, with this subgroup of patients developing less breast cancer.24 While the reasons for this increase in breast cancer among obese women is not completely understood, there are three plausible theories. These relate to elevated estrogen levels, elevated insulin and insulin-like growth factor (IGF) levels, and the chronic inflammatory state associated with obesity.
In the absence of ovarian function in the postmenopausal woman, estrogen production occurs peripherally as circulating and androgen precursors (androstenedione) are enzymatically converted. The key enzyme for this process is aromatase. Aromatase is found largely in peripheral adipose tissue as well as adipose within the breast and breast tumors.25 Increased adipose associated with obesity leads to increased aromatase and ultimately increased circulating biologically active estradiol.22,23,26 Tumor necrosis factor alpha (TBF-α) and interleukin 6 (IL-6) are secreted by adipocytes to increase aromatase production. These cytokines can work in an autocrine or paracrine fashion and thus also increase the local production of estrogen in the breast.27
Elevated estrogen levels seem to correlate with differences in breast cancer risk, with the highest levels associated with increasing risk. Several very large reviews have shown this to be the case,28,29 with some noting a nearly double risk in those with the highest estrogen levels.
Conversely, evidence has shown that increased exercise and physical activity may result in the lowering of serum estrone levels.30 This helps perhaps explain the relationship between exercise and improved outcome among cancer survivors and for the practicing clinician helps reinforce recommendations for a healthy active lifestyle to our breast cancer patients for good reason.
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