Self Study:Book Chapter Review & Reading Notes

Chapter 4: Pathology of Breast Disorders

Functional unit of the breast is the terminal ductal lobular unit.

The entire lobular and ductal structure of the breast is lined by two layers of cells:the inner epithelial layer and the outer myopepithelial layer.

“Breast cancer” typically refers to breast carcinoma that arises by preferential growth of the inner epithelial layer.

Benign Disorders:
Fibrocystic change-pathologic condition that correlates with ‘lumpy’ breasts.

This term is applied to a plethora of benign changes in the breast, which are best categorized based on the subsequent risk of development of breast carcinoma.

Three categories:

Non-proliferative lesions:
Proliferative lesions without atypia
Atypical hyperplasia

Nonproliferative Lesions

This is the most common category of breast disorders and includes cysts, papillary apocrine change, mild hyperplasia of the usual type, and epithelial-related calcifications.

Women with these lesions do not incur a higher risk of development of breast carcinoma than that of women who had no breast biopsy (relative risk, 0.89)

Proliferative Lesions without Atypia
Women with these lesions have a slight risk of developing breast carcinoma, 1.5 to 2 times greater than the general population. This category includes moderate or florid hyperplasia of the usual type, sclerosing adenosis, small duct papillomas, and fibroadenomas.

Sclerosis adenosis is the most common lesion and refers to expanded lobular units with a proliferation of both acini and intervening stroma. Microcalcifications are frequently seen and correspond to “benign calcifications” seen on mammography.

Atpical Hyperplasia

Atypical hyperplasia confers a risk of development of breast cancer that is 3.5-5 times that of the reference population. This category includes both atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH).

Radial Scars and Complex Sclerosing Lesions

Radial scars are typically small areas of scarring (less than 1 cm) surrounded by glandular elements.

Benign Neoplasms

Fibroadenoma

Fibroadenomas typically present as painless, mobile, rubbery masses. They are usually solitary but occasionally multiple. Most often present in the upper-outer quadrant and slightly more common in the left breast.

Solitary (Large Duct) Intraductal Papilloma
These tumors typically arise in a large duct in the subareolar region and present with unilateral hemorrhagic discharge.

Phyllodes Tumor

Character may be benign to malignant. Phyllodes tumors tend to have local recurrences and should be widely excised.

Lobular Carcinoma in Situ (LCIS)
LCIS is a rare multicentric entity that can not be identified clinically or on gross examination.

The invasive carcinoma that may develop may be either ductal or lobular.

LCIS is more common in younger, premenopausal women, and the mean age of diagnosis is 44 to 46 years.

LCIS is commonly bilateral and multicentric (present in more than one quadrant).

LCIS is typically an incidental finding in a breast biopsy done for a mammographically detectable lesion, which may be calcifications in adjacent sclerosing adenosis or other proliferative lesions.

Estrogen receptor (ER) is typically over expressed in cells of LCIS, whereas Her-2/neu is not. E-cadherin is a useful marker to distinguish lobular and ductal proliferations because it is preferentially expressed in ductal proliferations.

Most women with LCIS do not develop invasive carcinoma on follow-up, but it does confer a relative risk from 6.9 to 12. The carcinomas that develop are mostly invasive ductal carcinoma.

LCIS is best considered to be a risk factor rather than a precursor of invasive carcinoma. Thus, the surgical management of LCIS does not aim for negative margins, and radiation therapy has no role in management of LCIS.

Ductal Carcinoma in Situ

Ductal carcinoma in situ (DCIS) comprises lesions in which the neoplastic growth of ductal cells is restricted within the ductal system.

DCIS is considered to be a direct precursor of invasive carcinoma.

The incidence of carcinoma in patients with DCIS varies from 11% to 53% and occurs in the ipsilateral breast.

Mammographic abnormalities, which commonly show microcalcifications, are the most common presentation of DCIS.

Comedo DCIS refers to central necrosis in the ducts that are lined by poorly differentiated cells. Comedo DCIS is invariably associated with calcifications.

Comedo necrosis was the only factor found to correlate with ipsilateral recurrence in a multivariate analysis of nine histologic features of DCIS.

The distinction between LCIS and DCIS can usually be made with E-cadherin staining. E-cadherin shows no staining in lobular proliferations.

Low Grade DCIS tends to be ER and PR positive and Her2/neu negative.
High Grade DCIS tends to be ER/PR positive and Her2/neu positive.

Tamoxifen decreases recurrence rates in patients with DCIS.

DCIS specimens should be inked for margins. In NSABPB-17, only the presence of a tumor-filled duct in contact with the inked margin was categorized as a positive margin.

Silverstein et al. showed that quantification of the distance of DCIS from the margin is useful, and greater than 1 cm is deemed to be a negative margin.

Paget’s Disease of the Nipple

Association of eczematous changes in the nipple with underlying mammary carcinoma. Paget’s disease of the nipple refers to the extension of underlying breast cancer to the skin of the nipple.

Paget’s disease presents as scaling and erythema of the nipple-areola complex.

95% of cases of Paget’s have underlying carcinoma, invariably ductal, and often associated with comedo-type DCIS.

Immunohistochemical stains are useful to distinguish Paget’s from melanoma and clear cells of the epidermis.

Her2/neu, epithelial membrane antigen, and polyclonal CEA are expressed in Paget’s CK 7 is positive in both Toker cells and Paget’s disease.

Self Study: Book Chapter Review & Reading Notes

Chapter 3: Mammography of the Surgically Altered Breast

The Mammogram:Basic Principles:

Compression of the breast is important to separate structures, improve contrast and resolution, and minimize x-ray dose.

Standard mammogram two views of each breast:

The craniocaudal (CC) view is the projection from top to bottom.
The mediolateral oblique (MLO) view is the projection from side to side with the compression plates and x-ray tube angled obliquely parallel to the pectoralis major muscle to optimize imaging of the axillary tail.

By convention, the projection markers are placed toward the axilla in each view.
Signs of malignancy include:

A speculated lesion and calcifications that may be described at casting, granular, pleomorphic, or linear.

Other findings may include architectural distortion (speculations without central density), mass (which is usually ill defined but may be well defined), or an area of tissue asymmetry, not forming a three dimensional mass.

Studies:

A screening study is that which is performed on an individual in whom no disease is suspected.

A diagnostic study is that performed on an individual with physical signs or symptoms of breast cancer or whose screening mammogram results were abnormal.

Ultrasound is usually suggested when a cyst is a diagnostic possibility or to guide interventional procedures such as aspiration, biopsy, or abscess drainage.

Benign Biopsy Changes:

Dystrophic Calcifications
Spherical Calcifications

Imaging the Conservatively Treated Breast:
Breast conservation therapy following lumpectomy or segmentectomy with radiation therapy and axillary node dissection presents unique challenges to the radiologist who must discriminate treatment changes from recurrence and monitor for metachronous lesions.
Mammography and physical examination are complementary and should in all cases be used as first-line follow-up methods.

To establish a post treatment mammographic baseline, a unilateral examination is obtained of the post treatment breast at approximately six months after the initial diagnosis when surgery and radiation are completed.

Imaging the Postmastectomy Breast without Reconstruction:
In practice, there is typically insufficient tissue for mammographic evaluation, and standard compression mammography requires some amount of mobile tissue.

Any recurrence in the skin or chest wall are appreciated by physical examination. CT-scan or ultrasound may be helpful in evaluating any possibility of recurrence.

Imaging the Postmastectomy Breast with Implant Reconstruction:
There is usually little to no residual breast tissue after mastectomy. Placement of an implant obscures native tissue, only a small rim of native tissue remains. Other imaging modalities may therefore be used in conjunction with mammogram.

Imaging the Postmastectomy Breast with Autogenous Reconstruction:

The autogenously reconstructed breast involves transfer of tissue as a myocutaneous flap on a pedicle, as a free flap attached by microvascular techniques, or a combination.

There is no clearly established protocol for imaging the autogenously reconstructed breast. The reconstructed breast mound appears primarily lucent due to the fatty tissue.

The imaging is more useful in evaluating the more common occurrence of fat necrosis, which may present as a palpable abnormality and is a benign process. Benign dystrophic calcifications or lipid cysts may appear mammographically.

Imaging the Implant-Augmented Breast:

The breast, augmented with saline, silicone, or saline-covered silicone (double-lumen) implant, is an important imaging topic because the patient population who were in their 20s and 30s during the 1970s have now entered the mammographic screening population.

The normal implant appears as a radiodense oblong structure that may be subglandular or subpectoral. The margins are smooth. If the implant is double lumen, in many cases the density differences between the outer saline and inner silicone components makes these compartments radiographically visible.

Mammography may detect some proportion of implant ruptures, but only when loss of integrity results in some change in shape or volume that can be projected in tangent to the dense implant itself.

Intracapsular ruptures of silicone are mammographically occult.

Saline implant ruptures are typically clinically apparent as abrupt decompression and usually do not warrant further imaging.

Capsular calcification (unrelated to implant integrity) or a round configuration of the implant suggesting capsular contracture may also be observed mammographically.

Supplemental views of the breast have been developed to optimize imaging of native glandular tissues to screen for breast cancer. Displacement views developed by Eklund involves pushing back the implant while pulling forward the native tissues with sufficient diagnostic compression.

Native tissue may be obscured from the mammogram depending upon implant plane and the presence of capsular contracture.

Imaging the Postexplantation Breast:

Mammographic findings after implant removal are varied.

Serous fluid may fill the cavity and give the appearance of the implant itself. As this pocket matures and fibroses, masslike density with or without coarse calcification may develop. When the implant is removed without complication by rupture, the are may heal completely without identifiable scarring.

Postreduction Mammoplasty Breast:

Reduction mammoplasty is a commonly performed procedure:

Either:

To achieve breast symmetry (typically after surgical management of a contralateral breast cancer has resulted in breast asymmetry)
To relieve macromastia.

Mammogram should be obtained pre-operatively in the age-appropriate patient so an occult cancer can be excluded.

Once the procedure is done, a follow-up mammogram should be obtained in 1 year to reestablish the new mammographic baseline appearance.

Book Chapter Review Notes

Surgery of the Breast: Principles & Art. Editor Scott L. Spear. Associate Editors: Shawna C. Willey, Geoffrey L. Robb, Dennis C. Hammond, Maurice Y. Hahabedian.

Chapter 1. Incidence, Trends, and the Epidemiology of Breast Cancer.

Reading Notes: Part I.

Breast Cancer is the most common cancer among women in North America, representing 32% of all new female cancers.
Physicians from all specialties will commonly see women with breast cancer in their practices and should understand the etiology of the disease.

Trends in Breast Cancer Incidence, Stage at Diagnosis, and Mortality

Invasive Breast Cancer

In the United States, breast caner incidence has steadily increased, with a concomitant decrease in mortality.

Stage Distribution of Breast Cancer Cases:

1995 and 2000 -- 63% of women diagnosed with breast cancer had localized disease, 29% had regional involvement, and 6% were diagnosed de novo with metastatic disease.
Improved since: 1974 and 1985 -- when the incidences were 48%, 41%, 7%.

This supports the value of screening in providing early detection. Mortality has
decreased, evidenced by the increased use of mammography.

Ductal Carcinoma in Situ (DCIS)
Ductal carcinoma in situ (DCIS) is a noninvasive form of breast cancer that may progress to invasive disease if not detected and treated.
Prior to 1970 DCIS represented 3-4% of breast cancer diagnoses and most commonly presented as a palpable mass greater than 1 cm. in diameter.
DCIS now represents 25% of new breast cancer diagnoses, and most commonly presents as clustered microcalcifications detected mammographically. DCIS is 98% curable and early detection has contributed to the observed decrease in breast cancer mortality.
Because mastectomy is associated with both physical and emotional morbidity, breast conserving surgery has been studied in DCIS patients.

Lobular Carcinoma in Situ (LCIS)

Lobular carcinoma in situ increases the risk of cancer, but it is not a premalignant lesion. Instead, it is a marker of increased risk. The conclusion is drawn from the observations that most subsequent invasive cancers are infiltrating ductal, not lobular, carcinomas and that LCIS and invasive lobular carcinoma rarely coexist in the same specimen.
The risk of breast cancer when LCIS is present is bilateral, so management should address both breasts as a single organ. Because LCIS is premalignant, there is no role for lumpectomy, radiation therapy, unilateral mastectomy, or systemic chemotherapy.

Options for LCIS:

1. One option is frequent observation because some patients may not develop cancer. This management consists of breast examination every 3-6 months with yearly mammograms and prompt workup and/or biopsy of suspicious findings. This option is designed to detect cancer, should it occur, at the earliest possible stage and is not designed to prevent cancer.

2. A second option includes bilateral prophylactic mastectomy that removes tissue at risk.

3. A third option is a 5 year course of tamoxifen. In the NSABP P-1 study, the Breast Cancer Prevention Study, tamoxifen reduced the risk of breast cancer by 56%

Article Review

Article Review of "Re: Trends in the Treatment of Ductal Carcinoma In Situ of the Breast." Journal of the National Cancer Institute. 96(16):1258-1259, August 18, 2004.[CORRESPONDENCE] by Gordon F. Schwartz, Michael D. Lagios, Melvin J. Silverstein.

Synopsis: At the time the article was written, the management of DCIS was in evolution to include: Breast conservation therapy, the use of adequate excision alone without radiation therapy, and the avoidance of axillary lymph node dissection for the disease. The management of DCIS needs a dedicated team for mammographic pathologic correlation, specimen radiography, inking of margins, and thorough histologic examination.

Article Review

Review of "Breast Cancer Diagnosis and Prognosis in Augmented Women" Plastic & Reconstructive Surgery 118: 587-593, 2006 by Neal Handel & Melvin J. Silverstein."

Frequently in my practice I am asked by many women who desire breast augmentation or who have already had a breast augmentation and now want a lift, removal and replacement, or surgery for capsular contracture the following question:

Do breast implants impair my ability to detect breast cancer or increase my risk of getting breast cancer?

To answer this question and as part of my own self study, I read and reviewed an article in Plastic & Reconstructive Surgery 118: 587-593, 2006 by Neal Handel & Melvin J. Silverstein. I present here notes which are helpful for my own self study as well as for patient education during consultation:

Background:
--Breast enlargement surgery is popular. More than 334,000 women underwent elective breast augmentation in 2004.
--A woman in the United States has a 1 in 7 (13.4 percent) lifetime risk of developing breast cancer.
--There is no etiologic link between implants and breast tumors. Numerous studies show that the rate of breast cancer is not increased among augmented women, and some studies demonstrate lower than expected rates.
--However, because of the large number of women undergoing augmentation, there have been persistent concerns about possible adverse effects of implants on cancer detection and treatment.

Methods:
The authors reviewed their database of women with breast cancer and determined if there was a difference in breast cancer between augmented and non-augmented women.

Results:
--There was no statistically significant difference in stage of disease between augmented and non-augmented patients. The mean tumor size, recurrence rates, and breast cancer- specific survival were virtually identical in both groups.--Augmented patients were more likely to present with palpable lesions.

Conclusion:
Augmented and nonaugmented patients are diagnosed at a similar stage of breast cancer and have a comparable diagnosis. While implants may impair mammography, they appear to facilitate detection of palpable breast cancers on physical examination.