Case of second primary breast cancer in ectopic breast tissue and review of the literature

Abstract

Accessory breast tissue (ABT) is found in approximately 2%–6% of the female population and are subject to most of the physiological and pathological changes that occur in pectoral breast. Primary breast cancer occurring in ABT is a rare occurrence and a second primary breast cancer occurring in an accessory breast has never been reported. We report the case of a 60-year-old woman with a history of mastectomy for left breast cancer 5 years prior to presentation, who presented with an enlarging right axilla mass found to be a second primary breast cancer in an accessory tissue on biopsy. Many physicians are unfamiliar with the clinical presentation of accessory breast cancer due to the rarity of the condition and this ultimately results in delayed diagnosis and advanced disease at presentation. It is therefore prudent that physicians have a high index of suspicion when patients present with axillary masses.

Background

Accessory breast tissue (ABT) occurs in about 2%–6% of the female population¹; it is generally thought to result from failure of regression of the milk line (extending from axilla to groin area) during embryogenesis, but some authors have suggested that it may also develop from modified apocrine sweat glands.¹

Accessory breast tissue may contain all the components of a normal breast tissue and is subject to the physiological and pathological conditions that affect the normal (pectoral) breast tissue.²

Primary breast cancer occuring in ABT (ABTC) is rare and represents only 0.3%–0.6% of all cases of breast cancer² and the literature contains mostly case reports and case series (table 1). The incidence of (a second primary) breast cancer in the contralateral breast is estimated to occur in about 4% of breast cancer survivors^{3 4} and there are currently no reported cases of a second primary breast cancer in ectopic breast tissue in the literature.

Table 1.

Patient characteristics, tumour characteristics and treatment reported in eight accessory breast tissue cancer studies

Study	Number of patients	Patient age (years)	Patient race	Patient sex	Location of cancer	Histology	Stage/grade*	Surgery type	Radiation	Chemotherapy*	Axillary node dissection
Giron et al2	1	65	Caucasian	F	Axilla	ILC, ER+/PR+	T2N0M0, grade not reported	Wide local excision	Yes	No	Yes
Devine et al7	1	61	Not reported	F	Axilla	ILC, ER+/PR+	Stage not reported, grade II	Wide local excision	Yes	No	Not reported
Famá et al9	4	Not reported	Not reported	4F	Axilla Axilla Axilla Anterior chest	ILC ER+/PR+, infiltrating apocrine cancer, IDC, ER−/PR− IDC, ER+/PR+	T1N0M0, T1NxMx, T1N3M1, T1, N0, M0	Not reported	Yes No Yes Yes	Yes No Yes No	Yes No Yes Yes
Nihon-Yanagi et al14	94	26–88	Not reported, study conducted in Japan	89F 5M	86 axilla seven anterior chest one unknown	IDC: 52 out of 64, papillotubular 14 out of 64, solid tubular 15 out of 64, scirrhous 23 out of 64, ILC 2 out of 64, apocrine carcinoma 4 out of 64, ER+ 29 out of 47 PR+ 23 out of 40	Stage I: 22, stage II: 33, stage III: 15, stage IV: 0	Individual data not reported	13	51	Individual data not reported
Francone et al15	1	43	Caucasian	F	Anterior chest	IDC, ER+/PR+	T1N1M0 grade II	Wide local excision	None	Yes	Yes
Soto et al16	1	42	Not reported	F	Axilla	ILC, ER+/PR+	T1N1M0	Wide local excision	Yes	None	Yes
Zhang et al6	11	27–48	Not reported, study conducted in China	11 F	11 Axilla	IDC: 8 ILC: 3 ER+: 9, PR+: 7	Stage I: 2, stage II: 4, stage III: 4, stage IV: 1	Modified radical mastectomy: 2, wide local excision: 6	3 patients	11 patients	8
Evans and Guyton†12	90	Not specified	Not specified	Not specified	64 axilla 15 sternal 9 subclavian 2 labial	Not reported	Missing, inconsistent	Radical mastectomy: 17, radical mastectomy: 2, wide local excision: 26	11 patients	1 patient	40 patients

*Chemotherapy excluding hormonal therapy.

†Treatment information reported for only axillary ectopic breast cancer.

ER, oestrogen receptor; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; PR, progesterone receptor.

The clinical diagnosis of malignancy in ABT is often more dificult, as this tissue is not routinely included or easily identified on screening mammography or diagnostic ultrasonography (US) of the breast, and does not usually present with symptoms typically associated with breast cancer (ie, palpable breast mass, nipple discharge, skin distortion or breast pain).⁵ Lesions in axillary ABT may elude detection for some time or may be mistaken for other more common pathology in this location (ie, lipoma or other soft tisue tumours, lymphadenopathy, and inflammation or abscess).^{2 6 7} This often leads to a delay in diagnosis and has been associated with more advanced disease and worse prognosis at the time of diagnosis.^{6 8}

To date there are no clear established clinical guidelines for the screening and/or detection or management of ABTC^{9 10} and clinicians often use the guidelines for the management of pectoral breast cancer for patients with ABTC.⁹

We present a 60-year-old female patient who originally presented with a primary breast cancer in the left breast that was treated with mastectomy and saline implant breast reconstruction without additional chemotherapy or radiation. Five years after her initial diagnosis the patient presented with a second primary breast cancer in ectopic breast tissue in the contralateral axilla. To our knowledge, this is the first reported case of such occurrence in the literature.

The authors believe this case highlights the importance of maintaining a high index of suspicion for ABTC in patients who present with axillary masses

Case presentation

A 60-year-old Ashkenazi Jewish female patient was diagnosed with ectopic breast tissue in the right axilla in 1998, after presenting with a right axillary mass. She underwent an excisional biopsy of the mass which revealed breast tissue and atypical ductal hyperplasia.

The patient subsequently developed a T1bN0M0 adenoid cystic carcinoma of the left breast in 2015. At the time of that presentation, the patient did not have a personal history of lobular carcinoma in situ, or breast cancer and she had not received radiation to the chest. The patient reported menarche at age 12, she had had two pregnancies, the first birth at age 30. She underwent bilateral salpingo-oophorectomy at age 42 for endometriosis, however, she never used hormone replacement therapy. Her family history was significant for breast cancer in a sister at age 31 and 43 as well as two maternal aunts. She tested negative for BReast CAncer gene (BRCA) 1/2. Based on her strong family history, the patient elected to undergo bilateral mastectomy and breast reconstruction with saline implants at that time and received tamoxifen for 5 years without additional chemotherapy or radiation.

She now presented with a painless 2 cm mass in the lateral aspect of her right axilla (figure 1).

Figure 1.

Two centimetre palpable mass on medial aspect of the right axilla.

Her clinical examination did not reveal any other findings and no clinically appreciable lymphadenopathy in the right or left axilla, the supraclavicular region or neck. The rest of her physical examination was unremarkable.

Investigations

The patient underwent US of both axillae which revealed ABT in the right axilla containing an ill-defined hypoechoic solid mass measuring 1.1×0.6×0.5 cm with peripheral vascularity and increased local tissue stiffness (figures 2 and 3).

Figure 2.

Ultrasonography showing an ill-defined hypoechoic solid mass measuring 1.1×0.6×0.5 cm.

Figure 3.

Ultrasonography showing an ill-defined hypoechoic solid with peripheral vascularity and increase in local tissue stiffness.

US guided core needle biopsy of the mass revealed invasive ductal carcinoma (IDC) of breast origin. MRI with gadolinium contrast of both breasts and axillary/thoracic inlet regions showed a benign appearing lymph node in the left breast at 2 o’clock position that appeared unchanged compared with previous imaging, and an irregular 1.1×0.8 cm enhancing mass, located superficially in the right axilla (figure 4).

Figure 4.

MRI with gadolinium contrast showing enhancing mass in the superficial skin of the right axilla (green arrow).

¹⁸F-fluorodeoxyglucose positron emission tomography-CT (FDG-PET CT) demonstrated a hypermetabolic focus in the right axilla measuring 1.6 cm with peak standard uptake value (SUV) of 3.6 and additional uptake in the sigmoid colon, with peak SUV of 5.1 (figure 5).

Figure 5.

Positron emission tomography (PET)/CT showing hypermetabolic focus in the right axilla (blue arrow) and the sigmoid colon (green arrow).

Treatment

The patient underwent wide local excision of the right axillary lesion with radioactive seed localisation using an eliptical incision with inclusion of an island of overlying skin (figure 6). Sentinel lymph node biopsy was attempted using methylene blue dye but no lymph nodes were identified. Methylene blue dye was used over technetium-99m because the authors felt that the proximity of the ABT to the lymph nodes in the axilla would interfere with signal detection by the neo probe.¹¹ Since there was no clinical evidence of and imaging studies did not show axillary lymph node involvement, the authors felt that formal axillary dissection was not indicated.^{10 12}

Figure 6.

Mass excised with an elliptical incision with overlying skin.

Surgical clips were placed around the side and deep margins of resection.

Histopathology

Hisotological evaluation revealed a 1.5×0.7×0.5 cm, grade II invasive ductal carcinoma (IDC). All margins were negative for tumour invasion and there was no skin involvement (figure 7). Oestrogen receptor (ER) positive >90%, progesterone receptor (PR) positive >90%, Her2Neu negative and Ki-67 20%. This was consistent with a pathological stage of pT1c Nx M0. In addition, there was a 12 mm diameter grade III ductal carcinoma in situ (DCIS) with comedo-necrosis, solid and cribriform type (figure 8). Because her tumour was ER/PR positive and HER2Neu negative, she underwent genomic testing (oncotype Dx) with a recurrence score of 17.

Figure 7.

Invasive ductal carcinoma under light microscope ×100 magnification.

Figure 8.

Ductal carcinoma in situ under light microscope ×40 magnification. Intraductal epithelial proliferation with high grade nuclear atypia.

Based on the recommendations of a multidisciplinary tumour board, the patient was offered hormonal therapy with anastrozole and radiation (50 Gy dose) to the tumour bed/axilla. Chemotherapy was not indicated due to her low (oncotype Dx) recurrence score.

Outcome and follow-up

The patient was seen at 1 week and 6 weeks postoperatively. Her incision was healed, she had good range of motion of the right shoulder and there was no evidence of lymphoedema. She is scheduled to start radiation therapy and hormone therapy.

Discussion

Primary ABTC is rare and occurs in 0.3%–0.6% of all breast cancers. Similarly, only about 4% of breast cancer survivors are diagnosed with a second primary breast cancer on the contralateral side.^{1 2} There are currently no reported cases of second primary breast cancer in ectopic breast tissue.^{7 9 12}

In the case described in this paper, the histology of the primary breast cancer (adenoid cystic carcinoma) was different from the pathology of the second primary malignancy in the ABT on the contralateral side (invasive ductal carcinoma and DCIS), and the second primary lesion occurred 5 years after the first primary cancer diagnosis. This raises the possibilty of an inherited genetic predisposition to cancer in this patient⁴ particularly since PET/CT in this patient demonstrated findings suspicious for sigmoid colon neoplasm (figure 5).

Although this patient tested negative for BRCA 1/2, she may benefit from a multigene panel test which has been found to reveal less common mutations such as PTEN, ATM, PALB2 and CHEK2 in 1%–12% of BRCA 1/2 negative cases.¹³ This patient may also benefit from a colonoscopy to investigate the suspicious colon lesion seen on PET/CT.

There are currently no consensus guidelines for the surveillance of ABT and the management of malignant lesions in ABT. The National Comprehensive Cancer Network guidelines outline surveillance and management algorithms for pectoral breast cancer but this does not address ABTC.¹⁰ Most reported cases were managed based on established guidelines for pectoral breast cancer, with some authors emphasising more aggressive approach for axillary ABTC due to its proximity to axillary LN and concerns for early metastasis.^{6 11 14}

Studies report that patients with ABTC tend to present with more advanced disease at the time of diagnosis and overall worse outcomes.^{2 11} This has been attributed to a lack of systematic surveillance of ABT¹ and atypical presentation of the disease.^{6 8} Zhang et al reported in a case series of 11 patients with ABTC, more than 80% of their patients presented with stage 2 or higher disease, 45% of patients demonstrated axillary nodal disease, and 36% had distant metastasis (table 1).

Similarly, among 85 patients with ABTC in Japan, 52% presented with axillary nodal disease at the time of diagnosis.¹⁴ However, when comparing pectoral breast cancer and ABTC of similar stage and histology, the prognosis seems to be comparable.^{7 11} These findings highlight the importance of early diagnosis and treatment of ABTC and the potential need for a directed search for ABT in patients with pectoral breast cancer. Similarly, a diagnosis of primary ABTC should prompt a work-up for pectoral breast cancer and metastatic work up.²

Patients with ABTC are currently managed mostly according to pectoral breast cancer guidelines mainly by surgical resection with negative margins (with/without), sentinel lymph node biopsy and/or lymphadenectomy when clinically positive nodes are present, as well as by evaluation of receptor status, genomic testing when indicated, and adjuvant hormonal and/or chemotherapy/radiation therapy, as indicated.^{6 10 13} To minimise loco-regional recurrence, metastasis and/or additional future malignant lesions in remaining breast tissue, all cases of ABTC should be evaluated by a multidisciplinary team (comprising a surgeon, medical and radiation oncologist, geneticist) to address the following questions:

1. What is the extent of surgical resection—should only the lesion be removed or all ABT? Should sentinel node biopsy be performed, or should formal axillary dissection be carried out?

2. What is the optimal regimen for surveillance—should the contralateral side be included? Should screening for residual pectoral breast tissue be modified in any way with a history of ABTC? And should other areas of potential ABT be routinely followed up?

3. What is the optimal adjuvant therapy?

Given the relative rarity of ABTC, an argument can be made to enter all cases in a national registry to allow future systematic evaluation and the development of consensus guidelines. For now, treatment plans need to be individualised, taking into consideration the patient’s risk factors, tumour characteristics, the patient’s physiological state and life expectancy, and patient preference.

Patient’s perspective.

I was not expecting my first diagnosis of breast cancer. When it happened, I decided to be aggressive with the management especially with my family history of breast cancer and I opted for a bilateral mastectomy. Since then, I have been very compliant with my follow-up visits and surveillance MRI and mammograms. Six months prior to my most recent diagnosis of breast cancer, I had undergone my routine examination with my doctor, and nothing stood out of place. I felt a lot of frustration after I diagnosed of breast cancer following the development of a mass in my armpit. I thought I had done everything right and opted for the most aggressive approach for the management of my index breast cancer. I am grateful however that the ectopic breast cancer was diagnosed at an early stage before it had the chance to spread. At this time, I am very grateful and trying to live my life.

Learning points.

• Many physicians are unfamiliar with the clinical presentation, evaluation and management of malignancies in accessory breast tissue.

• Accessory breast tissue (ABT) is often not clinically apparent or included in routine breast cancer surveillance and patients with cancer occurring in ABT (ABTC) often present with a more advanced disease state.

• The diagnosis of ABTC should be considered in all female patients with axillary mass lesions, particularly those with a prior breast cancer diagnosis and/or significant risk factors.

• Work-up and treatment planning should be multidisciplinary and include the evaluation of all (including contralateral) breast tissue and potential areas for ABT.