Nipple Sparing Mastectomies

The surgical treatment of breast cancer has evolved from radical mastectomy with routine removal of the nipple-areolar complex (NAC) to breast conservative therapy with preservation of the breast and NAC. When breast conserving surgery is not appropriate due to tumour related factors or the patients desire is for a mastectomy (either for risk reduction or cancer indications), conventional therapy still consists of mastectomy with removal of the NAC, followed by reconstruction.

Rising interest in improved cosmesis has led to the introduction of the skin-sparing (SSM) and now nipple-sparing mastectomy (NSM) as potential alternatives to modified radical mastectomy.

Chasing the nirvana of the perfect breast reconstruction results in conflict between maintaining surgical oncological principles while chasing more aesthetically pleasing and possibly better functioning reconstructed breasts.

The current item up for debate is the concept of nipple sparing mastectomies. The nipple areolar complex is regarded as the signature of the breast or likened to the tip of a nose and has significant aesthetic impact and has both sexual and psychological importance due mainly to its nerve sensation (erectile ability, erogenous sensation). Emotive reasons for nipple sparing mastectomies may negatively influence the ability to accurately assess the procedure.

The current gold standard when required to do a mastectomy and reconstruction, is a skin sparing mastectomy and expander prosthesis reconstruction. This traditionally includes removal of the nipple areolar complex and the skin over the tumour (if required) so as to ensure clear surgical margins.

A reminder that SSM and prosthetic reconstructions should not be done in patients requiring radiation therapy as the complication rate is up to 50%.

There are three indications for SSM

	Patients who undergo the procedure for risk reduction (previously known as prophylactic mastectomies).
	Patients with duct carcinoma in situ (DCIS).
	Patient with invasive breast cancer.

Clearly in patients undergoing risk reducing surgery with diverse indications such as confirmed BRCA 1 and 2, strong family history of breast cancer, atypical ductal hyperplasia, lobular carcinoma in situ and other risk lesions have extremely low recurrence rates irrespective of whichever technique is used. The reason for this is that the actual incidence of these patients developing breast cancer post mastectomy cannot be accurately quantified.

Looking at retrospective studies on patients undergoing SSM for invasive cancer or DCIS, the nipple is affected by tumour cells in 5%-10% of cases.  

It is for this reason that the concept of nipple sparing mastectomies has been proposed.

There has been much controversy regarding the oncologic safety of NSM as well as the introduction of  a set of complications, such as nipple and areolar necrosis, that were  not a concern previously with total mastectomy. Complicating these issues is the data analysis, the lack of randomised control trials, no long term follow-up, and small isolated centre based retrospective audits.

There is evidence to suggest that breast cancers arise in the terminal duct/lobular units (TDLU), Small studies to determine the presence of TDLU in the nipple reveal most nipple papilla do not contain TDLU. In the small percentage that did, the TDLU were located at the base of the papilla. This however does not explain patients with Pagets Disease as well as DCIS or invasive cancers with spontaneous nipple discharges.

Tumour contra-indication for nipple sparing mastectomies that are currently being considered:

	Pagets Disease.
	Spontaneous nipple discharges with associated DCIS.
	Tumours close to the NAC.
	Multicentric breast cancers.
	Lobular breast cancers.
	Lymph vascular invasion.
	Inflammatory breast cancers.
	Over-expression of HER-2.

Patient contra-indications are smokers; relative contra-indications are patients with conditions resulting in poor blood supply or tissue healing (diabetics, systemic lupus and other connective tissue diseases).

Indications for nipple sparing vary from one institution to the next. The following indications have been taken from different institutions and are listed from safest to least safe.

	High risk patients for bilateral SSM, as a risk reduction procedure.
	Small isolated DCIS away from the NAC (? Definition of small).
	Small  invading breast cancers, with some institutes giving tumour size up to 3cm.
	Axillary ultrasound and sentinel lymph node negative.
	2cm distance from the nipple areolar complex.

Therefore only small cohorts of patients are eligible for this procedure on tumour based criteria.

The three criteria most associated with recurrence are:

	Tumour location central vs peripheral.
	Number of positive axillary lymph nodes.
	Lymphatic vascular invasion.

Patient assessment would require CAD mammography and MRI scan to exclude patients with multicentric disease or DCIs extending towards the NAC. The mammographic distance between the tumour and the nipple is independently predictive of NAC involvement and is useful as an equation variable. There is some suggestion that mammotome core biopsy (vac assist biopsies) may make this procedure even safer. My concerns with this, is mammtome core is a rather large needle biopsy and often results in a significant haematoma which may affect the nipple blood supply.

Looking at nipple sparing mastectomies in the risk reduction setting is critical as prophylactic mastectomy has been the subject of major publications by many international groups. Its oncology benefit is undisputed in patients with a genetic mutation. Nevertheless to recap the principles of this surgery, its impact on quality of life, its psychological, aesthetic, sexual, functional and pain repercussions are such that it should not and must never be offered in an emergency situation. Multi-disciplinary unit patient counselling involving discussions with other patients, onco-psychological assessment and discussions around the reconstruction should occur prior to patients undergoing the procedure. Immediate bilateral breast reconstruction by provisional or definitive implant with conservation of the skin flap and the nipple-areolar complex may constitute a positive radical issue for requesting and motivated patients at high genetic risk, managed by a multidisciplinary team. The incidence of cancer in the retained nipple after risk-reducing mastectomy is less than 1 per cent.

Technical problems with the procedure may be avoided by careful patient selection. Reconstructive difficulties would occur in patients who have large breasts or very ptotic breasts, and may require the use of mastopexy type skin sparing mastectomies. The nipple blood supply in these settings is often further compromised. Clearly the most significant concern is nipple viability followed by flap necrosis.

Clearly as with any procedure attention to careful patient selection and technical capability of the surgeon plays a role as well as understanding the learning curve associated with the procedure.

The lowest recurrence rates are seen in multi-disciplinary units that use intra-operative pathology after coring out the nipple to assess that the tissue is free of malignant or atypical cells.

Complications occurring are:

	Partial necrosis of the nipple with residual depigmentation.
	Sloughing of the nipple areola complex.
	Infection.

After dissection of all the breast tissue, the skin envelope with the areola is turned inside out and all milk ducts and any tissue beneath the areola are precisely dissected under the surgeon's visual control. Intra-operative pathological assessment of this retroareolar tissue next to the skin is performed using both imprint cytology and histology to decide whether the NA-skin can be preserved or not.

Incisions vary from centre to centre with areola crossing, and radial incisions being the most commonly used.Circumareolar/nipple-areola free graft, inframammary and crescentic mastopexy may also be used.

Immediate reconstruction can be performed with tissue expander placement or one stage implant latissimus dorsi muscle, transverse rectus abdominis muscle, or deep inferior epigastric perforator muscle flaps.

Studies looking at patient satisfaction with objective observer assessments are few. Important aspects to assess are appearance, symmetry, colour, position, and breast texture as well as nipple sensation and arousal. Most studies are small, and most patients are satisfied with the appearance, symmetry, colour, position of the nipple and the breast texture. However there is lower satisfaction amongst all patients with nipple sensation, most patients rating this as poor.

The largest study on nipple sparing mastectomy is from the European institute of Oncology in Milan which initially looked at intra-operative radiotherapy of the nipple areolar complex to decrease local recurrence. Unfortunately although the study showed that the local recurrence rates were not higher than usually observed the aesthetic and sensation of the NAC outcomes were poor. The abstract is attached for your information.

As always there are articles that push the boundaries even further. Endoscopic nipple sparing mastectomy has been proposed from units in Japan.

Although the studies are small and the oncological safety is reported as good the overall rate of nipple necrosis is unacceptably high.

Patient expectations must be addressed prior to the procedure, extensive pre-operative counselling and discussion needs to address expectations, aesthetic satisfaction, and long-term cancer control. Special emphasis needs to be made about decreased nipple areola sensation. Assessing the patient’s body image and personality typing prior to the procedure also ensures better patient satisfaction.

In patient requiring radiation who undergo nipple sparing mastectomy (NSM) with immediate autologous reconstruction (preferably latissimus flaps), oncological safety has not been evaluated. A higher incidence of local recurrence and decreased aesthetic results are seen, with more nipple areola complications.

In conclusion despite continued controversy and the need for more long-term outcome data, nipple-sparing mastectomy is a procedure that is gaining increasing visibility and acceptance. Provided that certain oncologic and practical criteria are applied, it has the potential for allowing less invasive surgery and improved cosmetic outcomes without increased oncologic risk in appropriately selected patients.