the management of paget’s disease of the breast

The Management of Paget’s Disease of the BreastElizabeth Marcus, MD, FACS

AddressDivision of Breast Oncology, John H. Stroger, Jr. Hospital of Cook County, Rush University, 1900 West Polk, Room 601, Chicago, IL 60612, USA.E-mail: [email protected]

Current Treatment Options in Oncology 2004, 5:153–160Current Science Inc. ISSN 1527-2729Copyright © 2004 by Current Science Inc.

IntroductionSir James Paget first described Paget’s disease of thebreast in 1874 [1]. He described a lesion that presentswith eczematous changes of the nipple, occasionallyassociated with bleeding and ulceration that wasa harbinger of underlying breast carcinoma. Paget’sdisease accounts for 1% to 3% of primary breastcancer cases [2•,3]. It is found to be associated withunderlying carcinoma, in situ or invasive, in most ofthe cases [4–7]. The prognosis is related to the stage ofthe underlying carcinoma.

The difficulty in developing a rational approachto the treatment of Paget’s disease is because of therarity of the condition. Most series in the literature are

retrospective, small in number (< 100 patients), and areaccrued over 10- to 30-year periods of time, duringwhich time, treatment options have evolved. Because itis difficult to amass large series of patients, it is difficultto engage in a randomized controlled trial to determinethe most efficacious treatment. It is even difficultto assemble a reasonably sized cohort of patients retro-spectively to guide treatment. However, retrospectiveand prospective series exist to guide therapeuticdecisions. In addition, information on treatment ofinvasive and noninvasive (ductal carcinoma in situ[DCIS]) breast cancer may be considered in developinga therapeutic strategy.

Treatment

• The primary treatment of Paget’s disease is surgical. Once a surgical proce-dure has been performed, adjuvant therapy is directed by the pathology of the underlying carcinoma. The central controversy in the care of Paget’s disease is whether the disease is amenable to breast conservation. The standard of care for many years for Paget’s disease has been a modified radical mastectomy. Performing a mastectomy removes the diseased

Opinion statementPaget’s disease of the breast is a relatively rare condition, accounting for 1% to 3% of primary breast cancers. It is associated with an underlying carcinoma, invasive or noninvasive (ductal carcinoma in situ), in most of the cases. Primary treatment is surgical with adjuvant therapy being dictated by the stage and nature of the underly-ing tumor. Modified radical mastectomy is the standard of care with breast conserva-tion appropriate in a select group of patients with Paget’s disease. This select group includes patients that are diagnosed with nipple-areola changes alone without evi-dence of a palpable mass or mammographic abnormality. In this group of patients, breast conservation offers local recurrence rates comparable to rates in patients with invasive or noninvasive cancers. In patients diagnosed with associated palpable masses or mammographic abnormalities suggestive of cancer, the recurrence rates are higher and mastectomy is warranted.

Surgery

154 Breast Carcinoma

nipple-areola complex and any underlying pathology. Because an underly-ing carcinoma (in situ or invasive) is found in most of the cases, a mastec-tomy offers excellent local control. In the era of breast conservation for in situ and invasive breast carcinomas, it is reasonable to question its applica-bility to the treatment of Paget’s disease. Several prospective randomized trials with mature follow-up data have shown the equivalence of breast conservation when compared with modified radical mastectomy in the setting of invasive and noninvasive (DCIS) cancer [8–10]. Because the prognosis of Paget’s disease is dependent on the stage of the underlying carcinoma, it is tempting to extrapolate the data from the treatment of invasive and noninvasive carcinomas to its treatment.

• Prospective trials of breast conservation in the setting of Paget’s disease are more difficult to perform. This is largely because of the rarity of the disease and the length of time required to amass a significant number of patients. Even retrospective series are difficult to accumulate and require multiple institutions to be involved or a lengthy period of time to be reviewed. Although no prospective randomized trials are found in the literature, prospective series of breast conservation for Paget’s disease do exist. In 1987, a prospective trial of breast conservation in patients with Paget’s disease was activated by the European Organization for Research and Treatment of Cancer [11••]. From 1987 to 1998, 61 eligible patients from multiple institutions were registered for this study. Patients had to have histologically proven Paget’s disease without any evidence of under-lying invasive carcinoma. Patients with noninvasive cancer (DCIS) were eligible. A cone excision, comprised of the removal of the nipple-areola complex and the subareolar breast tissue, was performed in each case. Histologically negative margins were required, with re-excision allowed as long as the size of the cone and re-excision was not more than 5 cm in width and depth. Patients received 50 Gy external beam radiotherapy to the whole breast in 25 fractions, and they underwent follow-up examina-tions until death. The study had a median follow-up time of 6.4 years (maximum 12.5 years), with 35 patients receiving follow-up for at least 5 years. Over this follow-up time, there were four local recurrences in the 61 patients (7%). Of those four recurrences, three (75%) were invasive and one was noninvasive (DCIS). The 5-year estimated local recurrence rate in this study was 5.2% (95% confidence interval, 1.8%–14.1%).

• Another large series (38 patients accrued from seven institutions over a 20-year period) of equally carefully selected patients (no associated palpable masses or mammographic densities) were treated with breast conservation and received follow-up prospectively. Actuarial local control rates were 91% at 5 years, 83% at 10 years, and 76% at 15 years. The 5-, 10-, and 15-year actuarial survival rates were 93%, 90%, and 90%, respec-tively [12••]. These results compare favorably with the results of breast conservation observed in large scale trials in the setting of invasive and noninvasive breast cancer [8–10].

Modified radical mastectomy

Standard procedure After induction of general anesthesia, the patient undergoes standard sterile prepara-tion and drape. An incision is fashioned that includes the nipple-areola complex in the skin ellipse that is to be removed. Skin flaps are made to the level of the clavicle superiorly, the sternal border medially, the latissimus dorsi laterally, and to the infra-mammary crease inferiorly. The breast is removed off the underlying pectoralis major muscle, taking the fascia with the specimen. The breast is reflected laterally and entry gained into the axilla. An axillary dissection is performed if there is evidence of invasive carcinoma. Alternatively, a sentinel lymph node biopsy may be performed to stage the axilla in the case of invasive carcinoma.

The Management of Paget’s Disease of the Breast Marcus 155

Contraindications A modified radical mastectomy should not be performed if there is no evidence of invasive carcinoma. The risks that accompany the performance of an axillary lymph node dissection are not warranted if the possibility of spread to the lymph node basin is low, which is the case in noninvasive carcinoma. Otherwise, there are no absolute contraindications to a modified radical mastectomy. The relative contra-indications include any condition that precludes the administration of a general anesthetic or carries with it a significant risk of mortality from the procedure compared to the risk of mortality from the underlying cancer. The patient’s overall medical condition must be assessed and life expectancy with and without treat-ment of the cancer estimated. The patient’s wishes concerning what is acceptable risk should play a central role in decision making.

Complications Complications include those related to the skin flaps on the chest wall, including bleeding, hematoma formation, infection, seroma formation, and flap necrosis. Complications may also result from the axillary node dissection, including injury to the long thoracic or thoracodorsal nerves, lymphedema (mild to severe, short term, or long term), skin numbness from severing intercostal brachia nerves, in addition to the risk of bleeding, infection, and hematoma or seroma formation at the axillary site.

Special points Patients who chose to have a modified radical mastectomy may also choose to have an immediate or delayed reconstruction. The options for reconstruction depend on those offered by a plastic surgeon and may include reconstruction with implants or autologous tissue. Patients who do not choose to undergo reconstruction can be fitted with a special postmastectomy bra and prosthesis. Some women chose not to have reconstruction or prosthesis. This is a personal decision that varies from patient to patient.

Simple mastectomy

Standard procedure A simple mastectomy is performed in the same manner as a modified radical mas-tectomy, with the exception of omitting an axillary node dissection. The procedure is terminated with the removal of the breast off the underlying pectoralis major muscle. Although a few lymph nodes may be found in the specimen in the tissue taken laterally, no formal dissection is performed. Reconstruction may be considered as part of the same operative procedure.

Contraindications Relative contraindications to a simple mastectomy include a prohibitive risk of general anesthesia, evidence of invasive disease that makes staging of the axilla desirable, and any medical condition that may make the risk of performing the procedure greater compared to the risk of undertreating the disease.

Complications The complications are similar to a modified radical mastectomy, except those compli-cations accompanying an axillary node dissection. The potential complications include bleeding, infections, hematoma or seroma formation, and flap necrosis.

Special points The patient has several options for the absence of the breast, including immediate or delayed reconstruction, the use of a prosthesis, or neither option. It is a personal choice.

Lumpectomy (breast conservation)

Standard procedure A lumpectomy may be performed using a variety of anesthetic techniques. Local anesthetic alone or in conjunction with sedation/monitored anesthesia care may be used. General anesthetics are used by some surgeons for all or selected cases. An incision is made in a curvilinear fashion in the upper half of the breast and in a radial fashion in the lower half of the breast for optimal cosmetic results. The area to be excised includes all gross disease, with an emphasis on obtaining a histologically negative margin. For Paget’s disease, the procedure will require resection of the entire nipple-areola complex or a segmental wedge of the complex with a cone of underlying tissue. The defect that is created is closed by simply closing the overlying skin. No attempt is made to reapproximate the deep tissues because this will result in a depression in the breast and a suboptimal cosmetic result. In the event that complete resection of the nipple-areola complex is required, the patient can consider subsequent reconstruction of a nipple and areola by a plastic surgeon.


Contraindications Lumpectomy is not appropriate for any patient in whom radiation therapy is not an option, which includes patients with connective tissue disorders precluding radia-tion therapy, patients with a history of previous radiation therapy to the area, and patients without access to appropriate radiation facilities. A series that retrospec-tively examined the use of lumpectomy/cone excision alone for Paget’s disease found unacceptable recurrence rates (5-year actuarial rate of 28% vs 5% compared to cone excision plus radiation therapy) [13]. Lumpectomy is also inappropriate if the volume of tissue that will need to be removed to obtain a histologically negative margin is too large to allow for the preservation of a cosmetically acceptable breast. Caution should be exercised in applying breast conservation to patients who are diagnosed with Paget’s disease with a mass or mammographic abnormality.

Complications Complications after lumpectomy primarily include the formation of a hematoma or seroma formation and the development of wound infections. Either complication can affect the ultimate cosmetic outcome.

Special points The underlying carcinoma in Paget’s disease is not necessarily confined to the retro-areolar space. The possibility of multifocality and multicentricity exists, which could potentially affect the ability to perform breast conservation and may adversely affect the recurrence rate. In one study by Kothari et al. [2•], despite 33% of the patients being diagnosed with a palpable mass, the malignant disease was confined to the retroareolar space in only 25% of the patients. Furthermore, in this study, the extent of disease was underestimated by mammography in 43% of the cases, potentially making selection of patients who are breast-conservation candidates more difficult. Another study by Kollmorgen et al. [5] reviewed 33 years of experience with Paget’s disease at Roswell Park Cancer Institute (Buffalo, NY) and found that a significant number of patients in their series (29%) had a peripherally located tumor that could potentially be missed by a wide local excision of the areola complex. Both of these series contained a significant number of patients diagnosed with an associated palpable mass with their nipple changes. In the series by Kothari et al. [2•], 23% of patients were diagnosed with palpable disease, with 86% of these patients showing invasive disease and 45% having nodal involvement. In the Roswell Park Cancer Institute series, 38% of patients were diagnosed with a palpable mass with nipple changes. Ninety-three percent of these patients were found to have an underlying cancer of which 75% was invasive. Fifty-seven percent of the patients diagnosed with a palpable mass were found to have axillary nodal metastasis. Both of these series concluded that a wide excision (lumpectomy), even in a negative margin, could provide inadequate therapy for patients with Paget’s disease. What these series actually raise is the issue of appropriate patient selection for breast conservation. In prospective series that have carefully selected the patients for conservation, patients with no palpable masses, or other densities by mammogram, the recurrence rates are no different compared to other series of breast conservation in patients with invasive or noninvasive cancer [3,11••,12••].

Skin-sparing mastectomy

Standard procedure The option of skin-sparing mastectomy has become available. With this procedure, an incision is made around the edge of the nipple-areola complex and the dissection is carried out through this limited incision. The nipple-areola is removed with the underlying breast tissue, but all of the other overlying skin is preserved. A recon-struction is performed immediately after the mastectomy. This reconstruction may be done with autologous tissue transfer or placement of an implant. Studies that have looked at the recurrence risk with skin-sparing mastectomy show no increase compared to standard mastectomy, making it an oncologically sound option for patients. In one large series of 539 patients treated with skin-sparing mastectomy and immediate breast reconstruction, the overall local recurrence rate with a mean follow-up time of 65.4 months was 5.5% [14]. Other studies have shown similarly acceptable local recurrence rates [15–17]. No studies have been performed specifi-cally examining the application of this technique with Paget’s disease, and because of the rarity of the disease, prospective studies are unlikely to be performed. How-ever, because the outcome of patients with Paget’s disease is dictated by the stage of the underlying cancer, it is reasonable to extrapolate the data from studies with invasive breast cancers to apply to this situation.


Contraindications Obvious skin involvement beyond the nipple-areola complex would preclude the use of this technique.

Complications Any complication that may accompany the performance of a mastectomy or immediate reconstruction is possible with this procedure, which includes bleeding, infections, wound healing problems, flap necrosis (native or transferred tissue), hematoma or seroma development, or problems with implant devices.

Special points Although there are skin-sparing mastectomies in which the nipple-areola complex is preserved because Paget’s disease involves the nipple-areola complex by definition, procedures that preserve this complex are inappropriate.

Axillary staging (axillary lymph node dissection/sentinel lymph node biopsy)

Standard procedure If the axilla has clinically palpable nodes, an axillary dissection is appropriate. In the setting of a clinically negative axilla, staging of the axilla is appropriate if the underlying carcinoma is invasive to direct the selection of adjuvant therapy. Axillary lymph node dissection or sentinel lymph node biopsy will stage the axilla. An axillary lymph node dissection may be done through the incision in the setting of a mastectomy or through a separate incision if a lumpectomy or skin-sparing mastectomy is performed. A standard level 1 and 2 dissection is typically performed for staging, with level 3 dissections reserved for patients with gross disease in level 2, which carries a high risk of occult level 3 disease, or level 3. Sentinel lymph node biopsy is performed with the use of radiocolloid, blue dye, or both at a variety of injection points (eg, peritumoral, periareola, and in the overlying skin), depending on the technique at the individual institution. A separate incision is made in the axilla overlying the suspected sentinel node and the hot and/or blue node is removed for pathologic examination.

Contraindications Relative contraindications include inability to withstand general anesthetic, the absence of invasive disease in which the risk of occult metastasis is low, and circumstances in which the information gained by staging of the axilla will not affect management or circumstances in which the value of the information is outweighed by the risk of the procedure.

Complications Complications for an axillary node dissection include development of a hematoma or seroma, injury to the long thoracic or thoracodorsal nerves, injury to intercostals brachial nerves with potentially permanent sensory changes to the skin of the upper arm, pain and restriction of range of motion, and the development of lymphedema. Lymphedema may be developed in the early postoperative period or may develop late, and it may range from mild to severe and may be permanent. Sentinel lymph node biopsy may decrease the risk of morbidity of axillary staging [18,19].

Special points Sentinel lymph node biopsy has emerged as an alternative to standard axillary node dissection for staging of the axilla. In institutions with adequate experience, a finding of a negative sentinel node is usually indicative that the patient has a node-negative breast cancer [20]. This procedure is appropriate for the staging of the axilla in a patient with invasive breast cancer, and it appears to be accurate even in the setting of multicentric and multifocal invasive breast cancers, which are often found with Paget’s disease [21]. In pure DCIS, there is not much of a role for sentinel lymph node biopsy, similar to axillary node dissection, because of the low incidence of lymph node metastasis in this setting [22]. Trials are ongoing to further define the role of sentinel lymph node biopsy, including additional valida-tion trials, trials examining the role of axillary lymph node dissection in a positive sentinel node, and trials to further define the role, if any, of sentinel lymph node biopsy in DCIS. The role of sentinel lymph node in Paget’s disease is unknown.

• Radiation therapy is used primarily as adjuvant therapy in the setting of breast conservation. Because of the rarity of the condition, there are no series specifically examining different techniques in the setting of Paget’s disease. Standard regimens are used in the literature when breast conserva-tion is attempted [3,11••,12••]. Radiation as primary therapy for Paget’s

Radiation therapy


disease, without resection, has been tried in carefully selected patients. In one series, 58 patients were identified over a period of 24 years who had Paget’s disease confined to the nipple-areola complex without clinical or radiologic signs of an associated intraductal or infiltrating breast tumor [23]. Twenty of these patients were treated with primary radiotherapy alone (17 of 20) or radiotherapy with limited resection (three of 20). Even with this carefully selected group of patients, the 7-year actuarial local recurrence rate was 19%, which is higher compared to series that included a standard lumpectomy with adjuvant radiation. Another series of primary radiotherapy in which patients were also carefully selected (no palpable mass or mammographic abnormalities) showed a local recurrence rate of 16%, with a median follow-up time of 5 years 3 months [24]. This rate is also higher compared to local recurrence rates expected with lumpectomy plus adjuvant radiation. Primary radiotherapy does not seem to be sufficient for routine treatment of this disease, while maintain-ing an acceptable local recurrence rate.

• There are no series specifically examining the role of radiation therapy after mastectomy in the setting of Paget’s disease. It is reasonable to extrapolate from the data available on the subject of postmastectomy radiation and use the stage of the underlying tumor to guide therapeutic decisions.

• Standard adjuvant regimens are used consisting of external beam radiation to the entire breast (range 50 Gy total dose). A boost to the tumor bed or remaining nipple-areola complex (eg, wedge resection) may be considered. Decisions concerning treatment to the supraclavicular, axillary, or internal mammary nodal chain should be made based on the stage and character-istics of the underlying cancer.

• All short- or long-term side effects associated with radiation therapy may occur in this setting.

• The outcome of Paget’s disease is determined by the underlying associated cancer. Therefore, the adjuvant treatment should be directed by the stage of the underlying disease. Standard markers should be assessed, including estrogen and progesterone receptors, with cerb2 status. These assessments may further refine decisions concerning adjuvant therapy. In one study of Paget’s disease, there was a higher rate of overexpression of cerb2 than would be expected in a series of other breast cancers [2•]. In that series, 83% of the patients with Paget’s disease overexpressed cerb2. Whether this is inherent in the tumor biology of Paget’s disease or something inherent in this particular series because of patient selection would require review of additional patients in other series. However, this result remains an intriguing finding and may suggest a role in this setting for agents targeting the cerb2 receptor. Additional studies of molecular markers in this disease are warranted to delineate the tumor biology of this disease and potentially improve the ability to tailor therapy for individual patients in the future. Reviewing adjuvant therapy for breast cancer, including chemotherapy, hormonal therapy, and biologic modifier therapy, is beyond the scope of this text.

Pharmacologic treatment


• As new technologies are developed for patients with breast cancer, it will need to be seen whether these therapies have applicability specifically to patients with Paget’s disease. Newer imaging modalities, such as magnetic resonance imaging, ultrasound, and positron emission tomography, may find use in further defining the group of patients in whom breast conserva-tion may be undertaken with acceptable recurrence rates. The evolving field of molecular biology may hold some keys to understanding the nature of this disease, identifying patients at high or low risk of recurrence, and selecting appropriate treatment strategies for individual patients.

References and Recommended ReadingPapers of particular interest, published recently, have been highlighted as:• Of importance•• Of major importance

1. Paget J: On disease of the mammary areola preceding cancer of the mammary gland. St. Bartholomew’s Hosp Rep 1874, 10:87–89.

2.• Kothari AS, Beechey-Newman N, Hamed H, et al.: Paget disease of the nipple: a multifocal manifesta-tion of higher-risk disease. Cancer 2002, 95:1–7.

Detailed pathologic examination of the breast in Paget’s disease, including distribution of the underlying carcinoma in the breast and the expression of cerb2 in Paget’s disease. The findings in this study may have implications for clinical management.3. Pierce LJ, Haffty BG, Solin LJ, et al.: The conservative

management of Paget’s disease of the breast with radiotherapy. Cancer 1997, 80:1065–1072.

4. Paone JF, Baker RR: Pathogenesis and treatment of Paget’s disease of the breast. Cancer 1981, 48:825–829.

5. Kollmorgen DR, Varanasi JS, Edge SB, Carson WE 3rd: Paget’s disease of the breast: a 33-year experience. J Am Coll Surg 1998, 187:171–177.

6. Chaudary MA, Millis RR, Lane B, Miller NA: Paget’s disease of the nipple: a ten year review including clinical, pathological, and immunohistochemical findings. Breast Cancer Res Treat 1986, 8:139–146.

7. Fu W, Mittel VK, Young SC: Paget disease of the breast: analysis of 41 patients. Am J Clin Oncol 2001, 24:397–400.

8. Fisher B, Anderson S, Bryant J, et al.: Twenty year follow-up of a randomized trial comparing total mastectomy, lumpectomy and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002, 347:1233–1241.

9. Veronesi U, Cascinelli N, Mariani L, et al.: Twenty year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002, 347:1227–1232.

10. Fisher B, Dignam J, Wolmark N, et al.: Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from National Surgical Adju-vant Breast and Bowel Project B-17. J Clin Oncol 1998, 16:441–452.

11.•• Bijker N, Rutgers EJ, Duchateau L, et al.: Breast conserving therapy for Paget disease of the nipple: a prospective European Organization for Research and Treatment of Cancer study of 61 patients. Cancer 2001, 91:472–477.

A prospective study of breast conservation in a carefully selected patient population. This study provides support for the use of conservation in patients with Paget’s disease presenting without a mass or associated mammographic abnormality.12.••Marshall JK, Griffith KA, Haffty BG, et al.: Conservative

management of Paget disease of the breast with Radiotherapy: 10- and 15-year results. Cancer 2003, 97:2142–2149.

A study of breast conservation in a good sized cohort with long-term follow-up time up to 15 years. Provides support for the use of breast conservation in a carefully selected group of patients diagnosed with Paget’s disease without a mass or mammographic abnormality.13. Polgar C, Orosz Z, Kovacs T, Fodor J: Breast conserving

therapy for Paget disease of the nipple: a prospective European Organization for Research and Treatment of Cancer study of 61 patients. Cancer 2002, 94:1904–1905.

14. Carlson GW, Styblo TM, Lyles RH, et al.: Local recurrence after skin-sparing mastectomy: tumor biology or surgical conservatism? Ann Surg Oncol 2003, 10:95–97.

15. Simmons RM, Fish SK, Gayle L, et al.: Local and distant recurrence rates in skin-sparing mastectomies compared with non-skin-sparing mastectomies. Ann Surg Oncol 1999, 6:676–681.

16. Spiegel AJ, Butler CE: Recurrence following treatment of ductal carcinoma in situ with skin-sparing mas-tectomy and immediate breast reconstruction. Plast Reconstr Surg 2003, 111:706–711.

17. Medina-Franco H, Vasconez LO, Fix RJ, et al.: Factors associate with local recurrence after skin-sparing mastectomy and immediate breast reconstruction for invasive breast cancer. Ann Surg 2002, 235:814–819.

18. Blanchard DK, Donohue JH, Reynolds C, Grant CS: Relapse and morbidity in patients undergoing sentinel lymph node biopsy alone or with axillary dissection for breast cancer. Arch Surg 2003, 138:482–487.

Emerging therapies


19. Golshan M, Martin WJ, Dowlatshahi K: Sentinel lymph node biopsy lowers the rate of lymphedema when compared with standard axillary lymph node dissec-tion. Am Surg 2003, 69:209–212.

20. Guiliano AE: Current status of sentinel lymphade-nectomy in breast cancer. Ann Surg Oncol 2001, 8(Suppl 9):52S–55S.

21. Tousimis E, Van Zee KJ, Fey JV, et al.: The accuracy of sentinel lymph node biopsy in multicentric and multifocal invasive breast cancers. J Am Coll Surg 2003, 197:529–535.

22. Intra M, Veronesi P, Mazzarol G, et al.: Axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast. Arch Surg 2003, 138:309–313.

23. Fourquet A, Compana F, Vielh P, et al.: Paget’s disease of the nipple without detectable breast tumor: conser-vative management with radiation therapy. Int J Radiat Oncol Biol Phys 1987, 13:1463–1465.

24. Stockdale AD, Brierley JD, White WF, et al.: Radiotherapy for Paget’s disease of the nipple: a conservative alternative. Lancet 1989, 2:664–666.

the management of paget’s disease of the breast

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