Journal of Aesthetic & Reconstructive Surgery

Keywords

Breast cancer; Nipple reconstruction; Mastectomy; Breast surgery

Introduction

There were approximately 2.1 million world-wide new diagnoses of breast cancer in 2018 [1]. This common disease will strike about 1 in 8 women. Data from 2017 shows approximately 252,710 patients to have newly diagnosed invasive breast cancer with 40,610 deaths from cancer in North America [2]. The diagnosis is made by history, physical exam, mammography, MRI (in selected cases), breast ultrasound, core biopsy with histological determination of molecular markers of estrogen receptors (ER), progesterone receptors (PgR), human epidermal growth factor receptors (formerly HER2 now ERBB2), and antigen Ki67. These markers are integral to the type of therapy that is chosen. The treatment for nonmetastatic breast cancer is to remove the tumor from the breast and regional lymph nodes to prevent metastasis and reoccurrence. A combination of therapies is used for the treatment of early breast cancer. It consists of local modalities, surgery, radiotherapy, systemic anticancer treatments and supportive measures all delivered in diverse sequences. The choice of treatment strategy is based on the tumor burden/ location (size and location of primary tumor, number of lesions, extent of lymph node involvement) and biology (pathology, including biomarkers and gene expression), as well as the age, menopausal status, general health status and preferences of the patient.

Psychological impact of breast cancer and mastectomy

The psychological aspects of a diagnosis of breast cancer are complex and far reaching. When a woman is diagnosed with breast cancer, a cascade of events with significant psychological impact begins. She must first cope with the diagnosis followed by treatment decisions all of which increase fear, anxiety, and depression. Since the breast is so important in the external (and frequently internal) identification of femininity, this diagnosis and treatment plan can have a devastating psychological impact. Women with breast cancer experience significantly poorer body image and greater rates of sexual dysfunction than do healthy women [3]. This may lead to feelings of self-consciousness, insecurity, inferiority, self-loathing, and sexual dysfunction, all which motivate many women to seek reconstructive surgery [4]. How each woman copes with this situation is based on a myriad of factors including overall health, state of mind, body image (especially as it relates to their breasts), femininity, sexuality, general anxiety, age, mental health, education, outlook on life, and general optimism. Treatment can take many forms but frequently involves mastectomy and/or radiation and chemotherapy, which adds to additional concerns of losing hair, recurrence of cancer, surgical complications, and losing a breast.

Mastectomy presents an unwelcome complex of psychological stress for a woman that is affected by multiple factors such as age, psychological well-being, general anxiety level, general health, medical history, extent and type of surgery planned, fear of additional cancer, fear of complications from the surgery, use of chemotherapy or radiation therapy, emotional relationships, sexual well-being, body image, and confidence in her surgical team [5,6]. These complex physical, social, medical, and emotional factors all interact with the outcome of the surgical procedure to make an impact on a woman’s quality of life. Sexual problems affect a significant number of these women and vary greatly, from 25 to 100 percent [7]. Sexual identity after breast cancer affects sexuality, body image, and frequently leads to self-loathing and relationship disturbances. Symptoms of sexual dysfunction in breast cancer patients is often exhibited by decreased libido, dyspareunia, vaginal atrophy and dryness, loss of breast sensitivity, and lowered sexual pleasure and satisfaction [8]. This is often coupled with considerable body shame and dissatisfaction, feelings of physical unattractiveness, and decreased self-esteem and femininity [9]. In order to prevent many of these sexual and psychological complications associated with breast surgery many women have been opting for reconstructive surgery [10]. This trend has increased for early stage breast cancer due to improved surgical reconstructive techniques with better cosmetic outcomes [11].

The nipple’s importance to the psyche

More in-depth research reveals that a woman’s body image, femininity, sexual libido and functioning, as well as psychological adjustment to her mastectomy are intimately linked to the preservation of the appearance and sensation of the nipples. Several studies have shown that preserving or reconstructing the nipple-areolar complex (NAC) creates a positive impact on body image and psychological adjustment in women with breast cancer. Body image is known to be a multidimensional concept that not only involves expectations with one’s appearance [12], but also body image disturbances and investment in appearance (which is the importance of body image in defining self-worth) [13]. Those women who have shown high appearance investment and low self-body image also show close association not only with self-esteem, but of general psychosocial functioning. It is widely agreed that body image is a prominent issue in a woman’s experience with mastectomy.

Although the treatment of breast cancer has significantly improved from the primary use of disfiguring radical mastectomy, with its potential of significant psychological scarring, to more conservative surgeries such as skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM), there is still a significant fear of treatment failure, with mortality, morbidity, and disfigurement as a possibility. As surgical techniques continue to evolve, SSM, which preserves the breast skin envelope, and NSM, which preserves the nipple, have been developed [14]. Following treatment, in an effort to feel like themselves again, patients often elect breast and nipple reconstruction. Breast reconstruction can take many forms (tissue expander, autologous flaps, SSM) and has been shown to have a positive psychological impact for patients. NSM has been the next advancement in this type of surgical oncology treatment. NSM is a derivative of SSM but uses thinner skin flaps and creates a 2-3 mm nipple-areolar flap [15]. NSM is only applicable to a small percentage of patients. The best candidates for NSM and direct-to-implant breast reconstruction are those women who want to keep their current breast size and have a defined breast ptosis (when the nipple is at or up to 1 cm below the crease {Grade I} or ptosis with the nipple at a level 1 to 3 cm below the crease {Grade II}) [16,17]. A woman’s psychological perception of her breasts as symbols of her femininity and attractiveness plays a big part in her decision to have reconstructive breast surgery [18]. The goal of NSM is to remove all the cancer, have limited surgical complications, and establish a more natural contour of the breast. It was also hoped to provide better projection and sensation, but frequently does not provide the wanted sensation or the optimum projection, so not fulfilling the cosmetic and subsequent psychological outcome, which would lead to the development of a better body image, feeling of self-worth, sexuality, and quality of life. This procedure is not even possible in many patients who have nipple involvement with induration, retraction, fixation, ulceration, pathologic nipple discharge, or Paget’s disease. This type of surgery is avoided if the tumor is close to the NAC, or if they have had prior breast surgery with periareolar incisions [19].

More recent research has shown that prophylactic NSM may actually provide a better long-term body image and sexual wellbeing for women compared with SSM. Those who chose the NSM procedure also did not experience higher distress over future breast cancer risk or other psychosocial functioning than the women who chose the SSM procedure [20]. In several studies with those patients who were eligible, NSM followed by post mastectomy reconstructive surgery has been found to provide a greater sexual and psychosocial-sparing well-being effect than those with SSM and reconstructive nipple surgery [21]. Zong has shown that there is a big difference in psychological outcomes if the NAC is spared during mastectomy rather than reconstructed at a later date under local anesthesia [22]. He found that patients exhibited lower satisfaction with a reconstructed nipple. In addition, Wei reported that psychosocial well-being and sexual well-being are lower in SSM compared to NSM [23]. The re-creation, by surgery and/or tattooing, of the nipple has a high correlation with overall patient satisfaction and acceptance of body image. Unfortunately, the long-term patient total satisfaction has been reported to be only 16% [24].

However, despite the tremendous increase in NSM, there is still controversy over the appropriate patient, the risk of surgery, preferred type of reconstructive surgery, and patient safety and satisfaction [25]. NSM has been found to have an incidence of less than 1% cancer in the retained nipple after risk-reducing mastectomy, but the rate of nipple necrosis varies from 8% for total necrosis to 16% for partial necrosis [26]. Reported rates of NAC and mastectomy flap necrosis range from 4.4% to 37.5% and 2% to 12.7% in the literature, respectively [27]. Established risk factors for NAC and mastectomy flap necrosis include elevated body mass index (BMI), smoking, preoperative radiation, incision placement, and mastectomy specimen weight, among others [28]. But many times after NSM the nipple will flatten. Before the nipple stabilizes, during the first 3 months as much as 30% of the nipple flattens [29].

In order to improve surgical outcomes, new regenerative medical technology has been developed to address many of these problems with reconstruction of the NAC. Nipple reconstruction is the crowning achievement of a successful breast reconstruction. However, diverse surgical techniques have been attempted to reconstruct the NAC with a decrease over time of nipple projection still being a problem. This causes a poor aesthetic result with a subsequent psychological impact of overall patient disappointment. Many surgeons have tried the insertion of alloplastic materials, such as calcium hydroxyapatite, polytetrafluoroethylene, or autologous tissue grafts, to prevent flattening with added support [30]. However, this can lead to increased operative times, pain, infection, and greater patient morbidity. Unfortunately, many of these are non-permanent, non-living nipples that do not have adequate depth or projection. Conventional techniques (autografts, CV flaps, etc.) and newer product techniques (Cook Biodesign Nipple Reconstruction Cylinder [NRC] and NSM) still do not provide adequate solutions for most patients. Conventional flaps lose 70% of projection in 1 year and NRC maintenance of nipple projection was only 37.3% at 1 year and only 30% of women studied had satisfactory sensation in their nipples [31].

Allogeneic acellular graft for NAC reconstruction

The next stage in the improvement of surgical techniques for breast reconstructive surgery is the development of the humanderived allogeneic acellular graft (AAC) for NAC reconstruction (Bio-Aesthetics NAC graft) (Figure 1).

Figure 1: Allogeneic acellular graft for NAC reconstruction.

The use of an AAC graft would allow these patients a living and permanent tissue engineering solution to nipple reconstruction [32]. The clinical application would be to replace nipples during reconstructive surgery and to enhance the aesthetic results.

This clinical application should help enhance mastectomy and the procedure may obviate the fear associated with cancer reoccurrence when the NAC is spared for cosmetic purposes. The use of nipple regeneration may also provide a more natural, safer alternative with better cosmetic and psychological results contributing to improvement in a patient’s quality of life. The idea that a woman’s own cells are helping to restore her breasts with a more “natural” nipple may be very appealing to some women and help provide a better image of them. The AAC graft is the first decellularized NAC for NAC reconstruction, and it preserves the extracellular matrix including insoluble protein and proteoglycan components [33]. Since it is acellular, it obviates the rejection risk and does not require an immediate blood supply to sustain the graft. These nipples regenerated by (AAC) graft should be able to maintain nipple projection and provide a better cosmetic result. This new product is in end stage development and could be the ultimate solution, by being available to more women and providing a safe, long-lasting nipple, without the increased potential of significant complications such as necrosis and the need for additional surgery. Thus far, promising preclinical data have been obtained and we look forward to observing its clinical performance. This regenerative graft has the potential to relieve some of the anxiety and psychological and sexual stress associated with mastectomies and their complications, and helps these patients obtain a better quality of life.

Discussion and Conclusion

The diagnosis of breast cancer with the need for surgery has major psychological implications since the breast is closely tied to a woman’s body image, femininity, and sexual well-being. In order to keep the breast as intact as possible, NSM with reconstructive surgery has been the most preferred surgical treatment. However, this is not possible in all women, and it may present risk of cancer recurrence in others. The cosmetic results are frequently not ideal, with the potential for flattening nipples, necrotic tissue, and the need for additional surgery. New technological breakthroughs are being developed to address this problem. A regenerative AAC graft has the potential to solve many of these problems and prevent much of the psychological stress that many women who undergo mastectomy endure.

References

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, et al. (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68: 394-424.
2. National Institutes of Health (1985) National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: female breast cancer. J Natl Cancer Inst 2: 1.
3. Male DA, Fergus KD, Cullen K (2016) Sexual identity after breast cancer surgery, sexuality, body image, and relationships. Palliat Support Care 10: 66-74.
4. Spencer K (1996) Significance of the breast to the individual and society. Plas Surg Nurs 16: 131-132.
5. Holland F, Archer S, Montague J (2016) Younger womenâ??s experiences of deciding against delayed breast reconstruction post-mastectomy following breast cancer: An interpretative phenomenological analysis. J Health Psychol 21: 1688-1699.
6. Schmidt JL, Wetzel CM, Lange KW, Heine N, Ortmann O (2017) Patientsâ?? experience of breast reconstruction after mastectomy and its influence on postoperative satisfaction. Arch Gynecol Obstet 296: 827-834.
7. Goldfarb SB, Dickler M, Patil S, Jia R, Sit L, et al. (2011) Sexual dysfunction in women with breast cancer: prevalence and severity. J Sex Med 66-72.
8. DeSimone M, Spriggs E, Gass JS, Carson SA, Krychman ML, et al. (2014) Sexual dysfunction in female cancer survivors. Am J Clin Oncol 37: 101-106.
9. Bouiren VM, Esplen MJ, Wong J, Toner B, Warner E (2016) Sexual functioning in breast cancer survivors experiencing body image disturbance. Psy Oncol 25: 66-76.
10. Wong SM, Chun YS, Sagara Y, Golshan M, Sager JE (2019) National Patters of Breast Reconstruction and Nipple-Sparing Mastectomy for Breast Cancer, 2005-2015. Anns Surg Onc 26: 3194-3203.
11. Sun B, Zenilman ME (2015) The swinging pendulum. JAMA Surg 150: 1-16
12. Cash TF (2012) Cognitive-behavioral perspectives on body image. Encyclopedia of Body Image and Human Appearance 334-342.
13. Cash TF (2004) The assessment of body image: An extensive revisiosn of the Appearance Schemas Inventory. Int J Eating Disorder 35: 305-316.
14. Toth BA, Lappert P (1991) Modified skin incisions for mastectomy: the need for plastic surgical input in preoperative planning. Plast Reconstr Surg 87: 1048-1053.
15. Zucca MG, Manconi A (2013) The evolution of mastectomies in the oncoplastic breast surgery era. Gland Surg 2: 102-106.
16. Cowel AS, Christensen JM (2017) Nipple-Sparing Mastectomy and Direct-to-Implant Breast Reconstruction. Plast Reconstr Surg 140: 44S-50S.
17. Kirwan L (2002) A classification and algorithm for treatment of breast ptosis. Aest Surg J 22: 355-363.
18. Spenser KW (1996) Significance of the breast to the individual and society. Plast Surg Nurs 16: 131-132.
19. Wagner JL (2012) Prospective evaluation of nipple areolar complex sparing mastectomy for risk reduction and early stage breast cancer. Ann Surg Oncol 4: 1-9.
20. Metcalf KA (2015) Long term psychosocial function in women with bilateral prophylactic mastectomy: Does presence of the nipple areolar complex make a difference? Ann Sur Oncol 22: 3324-3330.
21. Qureshi AA, Odom EB, Parikh RP, Myckatyn TM, Tenenbaum MM (2017) Patient-Reported Outcomes of Aesthetics and Satisfaction in Immediate Breast Reconstruction After Nipple-Sparing Mastectomy with Implants and Fat Grafting. Aesthet Surg J 37: 999-1008.
22. Zhong T, Antony A, Cordeiro P (2009) Surgical outcomes and nipple projection using the modified skate flap for nipple-areolar reconstruction in a series of 422 implant reconstructions. Ann Plast Surg 62: 591-595.
23. Wei CH, Scott AM, Price AN, Miller HC, Klassen AF, et al. (2016) Psychosocial and Sexual Well-Being Following Nipple-Sparing Mastectomy and Reconstruction. Breast J 22: 10-17.
24. Jabor MA, Shayani P, Collins DR, Karas T, Cohen BE (2002) Nipple-areola reconstruction: satisfaction and clinical determinants. Plast Reconstr Surg 110: 457-463.
25. Weber WP, Hugh M, Kurzeder C, Radisic VB, Koller R, et al. (2018) Oncoplastic Breast Consortium consensus conference on nipple sparing mastectomy. Breast Cancer Res Treat 172: 523-537.
26. Rusbey JE, Smith BL, Gui GPH (2010) Nipple-Sparing Mastectomy. J Surg 97: 305-316.
27. Frey JD, Salibian AA, Choi M, Karp NS (2017) Flap Thickness and Complications in Nipple-Sparing Mastectomy: Objective Evaluation using Magnetic Resonance Imaging. Plast Reconstr Surg 5: e1439.
28. Crompvoets S (2006) Comfort, control or conformity: women who choose breast re- construction following mastectomy. Health Care Women Int 27: 75-93.
29. Shestak KC, Gabriel A, Landecker A, Peters S, Shestak A, et al. (2002) Assessment of long-term nipple projection: a comparison of three techniques. Plast Reconstr Surg 110: 780-786.
30. Collins B, Williams JZ, Karu H, Hodde JP, Martin VA, et al. (2016) Nipple Reconstruction with the Biodesign Nipple Reconstruction Cylinder: A Prospective Clinical Study. Plast Reconstr Surg 4: e832.
31. Tierney BP, Hodde JP, Changkuon DI (2014) Biologic collagen cylinder with skate flap technique for nipple reconstruction. Plast Surg Int 1-6.
32. Pashos NC, Graham DM, Burkett BJ, O'Donnell B, Sabo RA, et al. (2020) Acellular Biologic Nippleâ??Areolar Complex Graft: In vivo Murine and Nonhuman Primate Host Response Evaluation. Tissue Eng 26: 872-885.
33. Graham D, Heim W, Caronna V, Chaffin A, Grasperge B, et al. (2019) A new approach to nipple reconstruction: In vivo evaluation of acellular nipple-areolar complex grafts. San Antonio Breast Cancer Symposium.