Breast cancer metastasizing to Jaw bones as the sole primary source: Systematic review

Abstract

Breast cancer has been known for its high propensity of metastasis to unusual locations and the jaw bones are one among those sites. Numerous studies examining metastatic tumours to the oral region have been described in the literature. However, the analysis of Breast cancer metastasis to the jaw bones alone has been the subject of relatively few published research studies to date. This review was conducted to examine the published cases of metastasis to jaw bones from breast cancer as the sole primary source from 1954-2023. An electronic search of the published literature was performed without publication year limitation in PubMed/ Medline, Scopus, Google Scholar, Web of Science, Science direct and Embase databases, using mesh keywords like (‘Breast cancer’, OR ‘Breast carcinoma’), AND (‘Metastasis’ OR ‘Metastases’), And (‘Jaw’ OR ‘Maxilla’ OR ‘Mandible’ OR ‘Temporomandibular joint’ OR ‘Condyle’). We also searched all related journals manually. The reference list of all articles was also checked. Our research revealed a total of 63 relevant papers with 74 patients. The mandible was more predominantly affected jaw than the maxilla. 20% of patients died with a mean survival time of 1.8 years. To conclude, Breast cancer metastasis to the jaw bones is a rare occurrence. Careful evaluation of more number of such cases is needed in order to raise awareness of these lesions and gain a better understanding of their characteristics.reful evaluation of such cases is needed to raise awareness of these lesions and gain a better understanding of their characteristics.

INTRODUCTION

Including cervical cancer, breast cancer (BC) is the leading cause of death among women. According to Global Cancer Observatory (GLOBACON) records, there were over 2.3 million new cases of BC worldwide in 2022, and this cancer was responsible for 684996 fatalities.[1] and the main reason for death is metastasis. Even in rare locations, the rate of metastasis is increasing. On the other hand, it has been noted that longer overall survival times for BC patients have been linked to improved treatment, new imaging methods, and early discovery. The most often affected organs in distant BC metastases are the brain, liver, lungs, and bones.[2] The most common neoplasm that has the potential to spread to the head and neck area is BC. It is uncommon for oral cavity metastases to occur and they can affect both osseous and soft tissues.[3] The most frequent source of cancer metastasis to the oral soft tissues (OST) is lung cancer (LC), while the most frequent source of metastasis to the jawbones (JB) is BC. Numerous research studies examining metastatic tumours to the oral region have been described in the literature.[3,4] However, the analysis of BC Metastasis to the JB alone has been the subject of relatively few published research studies to date. To better understand the characteristics of the documented cases of BC Metastases to JB in the literature from 1954 to 2023, a review of those cases was carried out.

MATERIALS AND METHODS

The present study was conducted by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. It was not necessary to obtain ethical approval for this review due to its nature.

Focused question

To answer the research question, “How many cases of BC metastasizing to JB have been documented in the literature, and what is the prognosis of these metastatic lesions?” the Joanna Briggs Institute’s CoCoPop (context, condition, population) paradigm was employed.

• Pop (Population): Patients with BC

• Co (Condition): Jaw bone metastasis

• Co (context): Characteristics of these patients (e.g., demographics, clinico-pathological and prognostic parameters, etc).

Search strategy for identification of studies

Without regard to publication year limitations, an electronic search of the published literature was conducted using mesh keywords such as (“Breast cancer” or “Breast carcinoma”) and (“Metastasis” or “Metastases”) and (“Jaw” or “Maxilla” or “Mandible” or “Temporomandibular joint” or “Condyle”) in the databases PubMed/Medline, Scopus, Google Scholar, Web of Science, Science direct and Embase [Figure 1]. We carefully searched every relevant journal as well. Every article’s reference list was examined as well.

Figure 1.

PRISMA flowchart showing search strategy

Screening of studies

Three stages of study screening were engaged in this review. First, duplicates were eliminated after two authors (SG, NA) separately assessed the titles. Subsequently, the selected abstracts of every report were independently examined by the next two authors (AV, RV). Based on how well they evaluated the titles and abstracts of the first 50 references they could find, the reviewers were calibrated. The reviewers' kappa value for agreement was 0.82. The abstracts and titles were included in the study if they satisfied the eligibility requirement. In the last round, authors (MEMH, FM) independently reviewed the texts of the chosen studies. All authors' cases that seemed to meet the inclusion requirements or for which there was inadequate evidence were gathered, discussed, and resolved in the final report.

Inclusion criteria

• Confirmed cases of JBM via BC. The cases reported were from years 1954 through 2023.

• Study types include retrospective analysis, case series, and case reports.

• Cases were chosen without regard to restrictions on demographics like age, gender, race, or socioeconomic status, among others.

• All published articles were included, regardless of language.

Exclusion criteria

• Cases with no definite diagnosis of JBM via BC.

• Publications from primary sites other than Breast that report the JBM.

• Cases with BC metastasis to OST, salivary glands, and maxillary sinus were not included.

• Research that did not offer individual patient information was disregarded.

• Editorials, conference abstracts, hypothesis papers, web news, media coverage, and animal experiments.

Outcome measures

Primary outcome measures: To evaluate the number of cases of JBM via BC reported in the literature and to determine their prognosis.

Secondary outcome measures: To evaluate other factors such as Worldwide distribution of cases, Patient’s demographic details, associated risk factors, Predominant site of JBM, Clinical features of these metastatic lesions, Most prevalent type of metastatic BC, Type of therapies used.

Risk of bias assessment

The majority of papers included in this review were case reports and case series. CARE and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklists were used to assess the likelihood of bias.[5,6] Numerous parameters needed for data extraction were missing from several studies. To get the full information on this bias, we attempted to get in touch with the authors of those cases, but we were unable to obtain the necessary data.

Data extraction and analysis

The data were extracted following the selection, screening, and in-depth inspection of the studies. Three tables [Tables 1-3] were created by tabulating and cross-checking the collected data. Six weeks were allowed to collect the data if any were missing. We then labelled the missing data as “Not available (NA)” in the text and the tables if the information was still lacking. Descriptive statistics were used to express the findings. By using Kaplan–Meier curves in survival analysis, the overall survival rate was determined.

Table 1.

Details of publications reporting cases of jaw bone metastasis from Breast cancer as the sole primary source (1954–2023)

Authors	Year	Country	Type of study	Total No. of patients	Reference No.
Salman and Langel	1954	USA	RA	1	7
Blackwood	1956	UK	CR	1	8
Epker et al	1969	USA	CR	1	9
Agerberg and Söderström	1974	Sweden	CR	1	10
Butler	1975	USA	CR	1	11
Mace	1978	UK	CR	1	12
Mizukawa et al	1980	USA	CR	1	13
Compere et al	1981	France	CR	1	14
Yagan et al	1984	USA	CR	1	15
Sailer and Makek	1984	Germany	CR	1	16
Sokolov et al	1986	Russia	CR	2	17
Abemayor et al	1988	USA	CR	1	18
Webster	1988	UK	CR	2	19
Boyczuk et al	1991	USA	CR	1	20
Lu and Chen	1991	Taiwan	CR	1	21
Franklin and Kunkler	1992	UK	CR	1	22
Stavropoulos et al	1993	USA	CR	1	23
Pruckmayer et al	1998	Australia	CS	5	24
Guimarães et al	2003	Brazil	CR	1	25
Staton et al	2003	USA	CR	1	26
Bodner et al	2006	Israel	RA	2	27
Duüker	2006	Germany	CR	1	28
Jia et al.	2006	China	CR	1	29
Miles et al.	2006	USA	CR	1	30
Fontana et al	2007	Italy	CR	1	31
Antunes and Antunes	2008	Brazil	RA	2	32
Menezes et al	2008	Brazil	CR	1	33
Osmola et al	2008	Poland	CR	1	34
Pannosian et al	2009	USA	CR	1	35
Santaolalla et al	2009	Spain	CR	1	36
Etrtas et al	2010	Turkey	CR	1	37
Patrica et al	2011	Brazil	CR	1	38
Gonzalez-Perez et al.	2012	Spain	CR	1	39
Qiu et al	2013	China	CS	1	40
AshabYamin et al	2014	Iran	CR	1	41
Della Cheisa et al	2014	Switzerland	CR	1	42
Erickson et al	2014	USA	CR	1	43
Varghese et al	2014	India	CR	1	44
Ram et al	2015	India	CR	1	45
Sudha et al	2015	India	CR	1	46
Thorawat et al	2015	India	CR	1	47
Azadeh et al	2016	Iran	CR	1	48
Cai et al	2016	China	RA	1	49
Loncarevic et al	2016	Serbia	CR	1	50
Aerden et al	2017	Belgium	CR	1	51
Dodo et al	2017	Japan	CR	1	52
Lu et al	2017	Taiwan	CS	4	53
Sahni et al	2017	USA	CR	1	54
Atsushi et al	2018	Japan	CR	1	55
Cmrecčak et al	2018	Croatia	CR	1	56
Hanc et al	2018	Turkey	CR	1	57
Nambiar et al	2018	India	CR	1	58
Ranka et al	2018	India	CR	1	59
Magat et al	2019	India	CR	1	60
Radovic et al	2020	Serbia	CR	1	61
Schulz et al	2020	Brazil	CR	1	62
Chang and Thambar	2021	Australia	CR	1	63
laaouze et al	2021	Morocco	CR	1	64
Liu et al	2021	China	CR	1	65
Madabhavi et al	2021	India	CR	1	66
Guha et al	2022	India	CR	1	67
Vetri et al	2022	India	CR	1	68
Ogura et al	2023	Japan	CR	1	69

CR=Case report, CS=Case series, RA=Retrospective analysis, UK=United Kingdom, USA=United states of America

Table 3.

Data describing treatment and prognosis of patients with Jaw bones metastasis from Breast cancer as the sole primary source (1954 to 2023)

Pt. NO.	Treatment Given	Prognosis	Survival time from diagnosis of metastasis to death (in months)
1	P	NA	NA
2	P	NA	NA
3	R	NA	NA
4	NA	NA	NA
5	P	NA	NA
6	S	D	NA
7	R	NA	NA
8	S	NA	NA
9	S	NA	NA
10	R	NA	NA
11	R	NA	NA
12	MT	NA	NA
13	NA	NA	NA
14	P	NA	NA
15	P	NA	NA
16	NA	NA	NA
17	NA	NA	NA
18	NA	NA	NA
19	NA	NA	NA
20	MT	Fav	-
21	P	Fav	-
22	P	D	6
23	P	D	12
24	P	D	20
25	NA	NA	NA
26	Died before Tt	-	-
27	MT	D	85
28	C	D	20
29	NA	NA	NA
30	R	Fav	-
31	NA	NA	NA
32	S	D	12
33	NA	NA	NA
34	NA	NA	NA
35	MT	Fav	-
36	NA	NA	NA
37	MT	NA	NA
38	H	Fav	-
39	MT	UFU	-
40	R	D	6
41	NA	NA	NA
42	MT	NA	NA
43	MT	NA	NA
44	R	Fav	-
45	Refused by patient	NA	NA
46	RTO	NA	NA
47	MT	Fav	-
48	MT	Fav	-
49	Died before Tt	-	-
50	MT	Fav	-
51	MT	LFU	-
52	NA	NA	NA
53	P	UFU
54	C	D	18
55	NA	Fav	-
56	NA	Fav	-
57	P	Fav	-
58	NA	D	36
59	RTO	NA	NA
60	MT	Fav	-
61	MT	Fav	-
62	RTO	D	6
63	P	Fav	-
64	MT	D	2
65	RTO	NA	NA
66	MT	Fav	-
67	R	Fav	-
68	NA	NA	NA
69	C	Fav	-
70	MT	D	36
71	MT	Fav	-
72	MT	Fav	UFU
73	MT	UFU	-
74	NA	UFU	-

C=Chemotherapy, D=Death, Fav=Favourable, H=Hormonal, LFU=Lost to follow-up, MT=Multiple therapies, NA=Not available, P=Palliative, R=Radiotherapy, RTO=Referred to oncologist, S=Surgery, UFU=Under follow up

Table 2.

Clinical data of patients with Jaw bones metastasis from Breast cancer as the sole primary source (1954 - 2023)

Pt. NO.	Age (in years)	Sex	PHOBC	Site of jaw	C/C	C/F	R/F	JBAISOM?	TOM (in months)	Other metastatic sites	Final diagnosis of BC	Side of BC
1	53	F	NA	Condyle (SNA)	Pain	Pain	OL	NA	NA	NA	IDC	NA
2	24	F	NA	Condyle (SNA)	Pain	Pain	OL	NA	NA	NA	PCC	NA
3	45	F	NA	Condyle (SNA)	Pain/swelling	Pain	OL	NA	NA	NA	NB	NA
4	46	F	Y	Condyle (L)	Left sided Preauricular pain	NA	NA	N	NA	NA	NA	NA
5	49	F	NA	Condyle (SNA)	Pain/Trismus	Pain	OL	NA	NA	NA	IDC	NA
6	54	F	Y	Condyle (L)	Limited MO	Limited movement	OB	N	48	Spin, pelvis	IDC	R
7	32	F	NA	Condyle (SNA)	Pain/Trismus	Pain	OL	NA	NA	NA	IDC	NA
8	65	F	NA	Condyle (SNA)	Pain/Trismus	Pain	OL	NA	NA	NA	IDC	NA
9	65	F	Y	Mand (R, P)	Pain/Swelling	NA	OL	NA	16	NA	IDC	R
10	56	F	NA	Condyle (SNA)	Pain/Trismus	Pain	OL	NA	NA	NA	IDC	NA
11	52	F	NA	Condyle (SNA)	Pain/Trismus	Pain	OL	NA	NA	NA	IDC	NA
12	54	F	NA	Condyle (SNA)	Pain/Trismus	Pain	OL	NA	NA	NA	NB	NA
13	NA	F	Y	Mand (SNA)	Pain	Pain	OL	N	12	N	CP	NA
14	52	F	NA	Condyle (SNA)	Pain/Trismus	Pain	OL	NA	NA	NA	NB	NA
15	54	F	NA	Condyle (SNA)	Pain/Trismus	Pain	OL	NA	NA	NA	NB	NA
16	NA	F	NA	Mand (SNA)	Pain	Pain	NA	NA	NA	NA	IDC	NA
17	NA	NA	Y	Mand (R, P)	NCS	Numbness, trismus, pain, paraesthesia	OL, Moth- eaten	N	NA	NA	IDC	NA
18	NA	M	NA	Mand (SNA)	NA	NA	NA	NA	NA	NA	NA	NA
19	55	F	Y	Condyle (SNA)	Pain	Pathologic fracture	OL	N	NA	NA	IDC	NA
20	74	F	Y	Mand (R, P)	Pain	Pain	OL	N	96	Bone	IDC	R
21	NA	F	Y	Mand (SNA)	Pain	NA	OL	N	180	MM	NA	NA
22	NA	F	N	Mand (SNA)	Pain	NA	OL	Y	-	MM	NA	NA
23	NA	F	N	Mand (SNA)	Pain	NA	OL	Y	-	MM	NA	NA
24	NA	F	N	Mand (SNA)	Pain	NA	OL	Y	MM	NA	NA
25	45	F	Y	Mand (L, P)	Swelling	Swelling	NA	N	5	N	ILC	NA
26	52	F	Y	Mand (SNA)	Rapidly growing mass	Tumor Mass	OL	N	12	N	CP	NA
27	47	F	Y	Mand (R, P)	Praesthesia of lip	Numbness	OL	N	NA	NA	IDC	NA
28	44	F	Y	Mand (R, P)	Parasethesia lip	Numbness	OL	N	NA	NA	IDC	NA
29	60	F	NA	Condyle (SNA)	Pain/Trismus	Pain	OL	NA	NA	NA	NB	NA
30	46	F	Y	Condyle (L)	NCS	Trismus	OL	N	132	MM	IDC	R
31	NA	F	Y	Condlyle (BL)	Pain	Pain	OL	N	NA	NA	IDC	NA
32	69	M	Y	Mand (SNA)	Pus discharge	Fistula	OL	N	48	NA	IDC	NA
33	62	F	Y	Mand (SNA)	Pain	Pain	NA	N	NA	NA	IDC	NA
34	36	F	Y	Mand (SNA)	Pain	Pain	NA	N	NA	NA	IDC	NA
35	42	F	Y	TMJ (R)	Pain	Swelling, Crepitations	OL	N	48	N	IDC	NA
36	NA	F	Y	Mend (L)	Pain	Pain	OL	N	12	NA	NA	NA
37	79	F	Y	Condyle (SNA)	Pain/swelling	Pain/swelling	OL	N	NA	N	IDC	NA
38	94	F	Y	Mand (R, P)	Tumor mass	Non tender, hard mass	OL	N	312	NA	IDC	BL
39	36	F	Y	Mand and Max (L)	Swelling, pain, numbness	Hard swelling	OL	N	24	MM	IDC	NA
40	51	F	Y	Condyle (R)	Pain, trismus	Swelling	OB	N	NA	Spine	IDC	NA
41	73	M	NA	Condyle (L)	Painful swelling	Swelling	OL	NA	NA	N	IDC	NA
42	47	F	Y	Condyle (SNA)	Painful swelling	Swelling	OL	NA	NA	N	IDC	NA
43	38	F	Y	Mand (R, P)	Pain	NAD	OL	N	24	NA	IDC	L
44	48	F	Y	TMJ (BL)	Painful swelling	Swelling	OL	N	144	NA	IDC	L
45	58	F	N	Mand (R, P)	Nonhealing extraction socket	Swelling	OL	Y	-	Ileac bone	IDC	NA
46	40	F	Y	Mand (L, P)	Swelling	Hard, non-tender, localized, round swelling	OL	N	24	Vertebrae	IDC	L
47	50	F	Y	Mand (R, P)	Painful Swelling	Pain, Swelling	OL	N	48	N	IDC	L
48	56	F	Y	Mand (L, A)	NCS	NAD	OL	N	48	MM	IDC	R
49	45	F	Y	Mand (R, P)	Painful Swelling	Swelling	OL	N	36	Skull	IDC	L
50	49	F	Y	Mand (L)	NCS, Paraesthesia	Tender Mass	OL	N	6	N	IDC	L
51	51	F	Y	Mand (P)	Pain, swelling, numbness	Pain	OL	N	NA	N	IDC	NA
52	60	F	Y	Mand (BL)	NCS	Numbness, Pain	OL	N	NA	N	NA	NA
53	54	F	Y	Mand (R, P)	NCS	Bony elevations	OL	N	108	MM	IDC	NA
54	55	F	Y	Condyle (L)	Trismus	Reduced MO	OL	N	1	MM	NA	NA
55	43	F	N	Mand (BL)	NCS	Pain	OL	Y	-	N	NA	NA
56	55	F	N	Mand (BL)	NCS	Pain	OL	Y	-	N	NA	NA
57	35	F	N	Mand (L)	NCS	Pain	OL	Y	-	N	NA	NA
58	59	F	N	Mand (L)	NCS	Pain	OL	Y	-	Brain	NA	NA
59	65	F	Y	Mand L (Complete)	NCS	NAD	OL	N	240	Lung, Vertebrae	IDC	L
60	76	F	Y	Condyle (R)	Pain	Pain, swelling	OL	N	36	N	IDC	L
61	76	F	Y	Mand (Whole)	Pain, swelling	Pain, swelling	OL	N	132	N	ILC	L
62	80	F	Y	Mand (R, AP)	Pain, Numbness	Swelling, Reduced MO	Moth eaten	N	192	NA	IDC	R
63	58	F	N	Mand (L, A)	Pain, Numbness	Paraesthesia	OL	Y	-	MM	IDC	L
64	50	F	N	Mand (R, P)	Pain, Swelling, Ulcer	Firm swelling	OL	Y	-	Lung	IDC	BL
65	40	F	Y	Mand (BL)	Paraesthesia	NAD	OL	N	6	Vert	ILC	R
66	62	F	Y	TMJ (R)	Tumefaction	Pain, Reduced MO	OL	N	24	N	IDC	R
67	52	F	Y	TMJ (L)	Pain	Pain	OL	N	14	N	NA	NA
68	56	F	Y	TMJ (R)	Difficulty in MO	Pain, Reduced MO	OL	N	120	N	IDC	R
69	64	F	Y	Mand (R, P)	Difficulty in MO, Tumefaction	Pain, Swelling	OL	Y	Same time	Sacroileal bone	IDC	R
70	44	F	Y	Max (R)	Bleeding from oral cavity	Massive bleeding	OL	N	48	MM	IDC	L
71	65	F	N	Max (L, P)	Pain and swelling	Tender, Firm swelling	OL	Y	-	NA	IDC	L
72	66	F	N	Mand (R, P alveolus)	Nonhealing ulcer, pain swelling for 1 month	Firm, indurated swelling	OL	Y	-	MM	Mucinous	L
73	37	F	N	Mand (R, P)	Bony tender swelling	Painful swelling	Rarefaction	Y	-	MM	IDC	R
74	83	F	Y	Mand (R)	Numbness and pain	Pain	OL	N	NA	NA	IDC	NA

A=Anterior, BC=Breast cancer, BL=Bilateral, CC=Chief complaint, CP=Cystosarcoma phyllodes, F=Female, IDC=Invasive ductal carcinoma, ILC=Invasive lobular carcinoma, JBAISOM=Jaw bones as initial site of metastasis, L=Left, M=Male, Mand=Mandible, Max=Maxilla, MM=Multiple metastasis, Mon=Months, MO=Mouth opening, N=No, NA=Not available, NAD=No abnormality detected, NCS=Numb chin syndrome, OB=Osteoblastic, OL=Osteolytic, PCC=Polygonal cell carcinoma, PHOBC=Previous history of breast cancer, P=Posterior, R=Right, R/F=Radiographic features, TMJ=Temporomandibular joint, TOM=Time of metastasis, Y=Yes

RESULTS

A total of 63 relevant papers were found using our research approach.[7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69] There were 74 patients in total, with 70 females and 3 men and a female to male ratio of 23.3:1. The USA accounted for the greatest number of instances (n = 13), followed by India (n = 10), Australia and Brazil (n = 6) and China (n = 4). The patients’ mean age was 54.4 years (range 24–94). The mean age was 71 years in males and 53.8 years in females. 17.6% of patients had no prior history of BC, compared to 62.2% who had. Compared to the maxilla (2.7%), the mandible (58.1%) was the most often affected jaw. In 28 cases involving the temporomandibular joint (TMJ), the condyle accounted for 31% of the metastatic deposit sites. There was a case involving both the mandible and maxilla. The maxilla showed equal involvement, although the left side of the mandible was more impacted than the right. Most of the cases didn’t reveal the side of involvement in both jaws. JB was the only site of metastasis in 25.6% of patients, while it was the initial location in 19% of cases. The time of detection of metastasis from mastectomy was one month to 17 yr. Pain (34%) and edema (27%) were the most predominantly noticed clinical symptoms. On radiography, osteolytic (OL) lesions were seen in 65% of cases. Invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) were the most common types of BC diagnosed. Major therapeutic aids included were multiple therapies (27%) followed by palliative (16.2%). A total of 20% of patients died with a mean survival rate of 1.8 years [Table 4].

Table 4.

Summary of results documented from literature research describing the characteristics of jaw bone metastasis from breast cancer as the sole primary source (1954 -2023)

Feature	Number
Total number of papers published	63 •Case reports-56 •Case series- 3 •Retrospective analysis -4
Total number of patients	74
World-wide distribution of cases	•USA-13 (17.6%) •India-10 (13.5%) •Australia=Brazil- 6 (8.1%) •Taiwan=UK-5 (6.7%) •China=4 (5.4%) •Japan -3 (4%) •Israel=Iran=Germany=Russia=Serbia=Spain=Turkey-2 (2.7%) •Belgium=Croatia=France=Italy=Morocco=Poland=Sweden=Switzerland-1 (1.3%)
Gender	•F- 70 (94.6%) •M -3 (4%) •NA-1 (1.3%) •F: M=23.3:1
Average age of patients (Mean, Range)	•Total- 54.4+/−53.5 (24-94) •M- 71 (69-73) •F- 53.8+/−52.5 (24-94)
Previous history of BC	•Y- 46 (62.2%) •N –13 (17.6%) •NA-15 (20.3%)
Jaw involved in metastasis	•Mand- 43 (58.1%) (R-17. L-9 . NA-13, BL-4) (A-2, P-19, AP-2, NA-20 •Max- 2 (2.7%) (R-1, L-1) (P-1, NA-1) •TMJ -5 (6.7%) (R-3, L-1, BL-1) •Condyle -23 (31%) (R-2, L-5, BL-1, NA-15) •Both Mand and Max-1 (1.3%)
Jaw bone as the initial site of metastasis	•Y- 14 (19%) •N- 43 (58%) •NA- 17 (23%)
Any other site of metastasis	•Y-24 (32.4%) •N- 19 (25.6%) •NA- 41 (55.4%)
Average mean time JBM metastasis after BC	•75.8+/- 48 •1 Month-26 Yr.
Clinical features	•Pain-25 (34%) •Swelling-20 (27%) •NCS- 15 (20.2%) •Reduced MO-7 (9.5%) •NA-6 (8%) •NAD-4 (5.4%) •Fistula-1 (1.3%) •Bleeding-1 (1.3%) •Bony elevations-1 (1.3%)
Radiographic appearance	•OL-63 (85%) •OB- 2 (2.7%) •Moth eaten-2 (2.7%) •Rrefaction-1 (1.3%) •NA-6 (8%)
Final diagnosis of metastatic BC	•IDC-48 (65%) •ILC-3 (4%) •CP-2 (2.7%) •PCC-1 (1.3%) •MC-1 (1.3%) •NA-14 (19%) •NB- 5 (6.7%)
Spread of BC	•IL-12 (16.2%) •CL-9 (12.2%) •BL-2 (2.7%) •NA-48 (64.8%)
Treatment aids	•Multiple therapies-20 (27%) •Palliative=12 (16.2%) •Radiotherapy-8 (11%) •Surgery-4 (5.4%) •Chemotherapy-3 (4%) •NA- 19 (25.6%) •RTO-4 (5.4%) •DBT-2 (2.7%) •Hormonal-1 (1.3%) •RBP-1 (1.3%)
Prognosis	•Favourable- 20 (27%) •Deaths- 15 (20%) •UFU- 4 (5.4%) •NA-34 (46% •LFU-1 (1.3%)
Average mean time of death from diagnosis of JBM (range)	21.5+-15 two month-7 yr.

A=Anterior, BC=Breast cancer, BL=Bilateral, CL=Contralateral, CP=Cystosarcoma phyllodes, DBT=Died before treatment, F=Female, IL=Ipsilateral, JBM=Jaw bone metastasis, L=Left, LFU=Lost to follow up, M=Male, Mand=Mandible, Max=maxilla, MC=Mucinous carcinoma, Mon=Months, N=No, NA=Not available, NB=No biopsy, NCS=Numb chin syndrome, OB=Osteoblastic, OL: Osteolytic, P=Posterior, PCC=Polygonal cell carcinoma, R=Right, RTO=Referred to oncologist, UFU=Under follow up, UK=United Kingdom, USA=United states of America, Y=Yes, Yr.=years

DISCUSSION

BC is one of the most deadly causes of death in females. Although the majority of instances are documented in females, a few cases of BC in males have also been described. The peak age of occurrence is the second to sixth decade in females.[60] In the current study, the average range of occurrences was from the second to the ninth decade, with 70 cases (94.6%) involving females and only 3 cases (4%) including males. The number of cases of BC metastasis has decreased over the past many years due to widespread imaging technologies and early identification, but the risk remains high.

Oral cavity metastases account for about 1% of all oral cancers and are regarded as uncommon. Metastatic lesions are considered to be a diagnostic challenge due to their uncommon nature and unusual clinical and radiographic appearance, which may lead to a false diagnosis of pathologic entities with a dental origin. The most common source of metastases to JB is BC. If this happens, the mandible is more likely to be affected than the Maxilla.[3] Based on existing research, Salman and Langel reported the first case of JBM from British Columbia in 1954.[7] Since then, just 74 of such cases have been documented in the previous 69 years (1954–2023). The mandible, with a predominance of the posterior and left side, was the site of JBM more frequently than the maxilla, while only 2 cases involved the maxilla.

Uncertainties exist regarding the pathogenic mechanisms underlying JBM. Tumour cells separate from their original site during the multistage process of metastasis and move via hematogenous or lymphatic routes to a secondary site.[4] The “Batson’s plexus,” a valveless prevertebral venous plexus network that involves retrograde tumour cell transit from the lungs to the face, is one of the suggested paths.[3] The most common method of metastasis in this case is hematogenous since the JB lacks lymphatic capillaries. Rich capillary networks serve as the environment in which tumour cells are found. Because blood flow control is regulated slowly in red bone marrow compared to fatty marrow, metastatic foci are more numerous in the former and allow increased entrapment of metastatic cells. Growth factors found in red bone marrow may also hasten the colonization of some metastatic tumor cells. Due to the presence of extensive red marrow in the mandible and predominantly fatty marrow in the maxilla, JBM is more common in the mandible (posterior part, especially the body [premolar-molar region], angle, and ascending ramus) than in the maxilla.[3] BC spreads to the JB primarily using the hematogenous pathway.

TMJ is an uncommon site of metastasis that is typically associated with skeletal metastases and develops in the latter stages of the disease. TMJ and condylar involvement were the least common among the JBM, according to Irani et al.[3] The actual explanation of the infrequent incidence of metastasis in the condylar region is unknown but is assumed to be owing to weak red marrow and deficient blood supply from the maxillary and temporal arteries. Moreover, tumour cell entrapment may be lessened by the existence of a bone plate in the condylar region, which could restrict tumour cell multiplication.[52] The most common causes of condylar metastases are initial tumours of the lung, breast, and prostate. However, there also have been cases of metastatic spread to the condyle from other organs, including the liver, stomach, colon, kidney, pancreas, etc. According to current research, 28/74 cases involved TMJ, of which 23 included condyle.

Because JBM resembles primary oral cancers, is located centrally, is asymptomatic, and has non-specific radiographic characteristics, it is more difficult to detect than OST lesions. Moreover, some anomalies may go unnoticed at autopsy since the jaws are not often examined. The actual incidence of metastatic tumours in the jaws may, therefore, be higher.[3]

JBM is of high clinical importance because it may be the only symptom of an undiagnosed underlying malignancy or the first sign of metastasis. Metastasis can even appear in patients after a prolonged disease-free period. In our study, JB was the initial site of metastasis in 19% of cases, whereas, in 58% of cases, metastasis was detected after the mastectomy was done for BC, with an average mean time of one month to 27 years.

Clinically, painful or asymptomatic swelling combined with dysphagia, paraesthesia, pathological fractures, numb chin syndrome, and trouble chewing are the hallmarks of metastatic BC to JB.[52] Pain and oedema were the two most common clinical characteristics seen in this study. These metastatic lesions can become challenging to diagnose due to their diverse appearance, which closely resembles periapical and odontogenic lesions, JB tumours, and numerous inflammatory illnesses of the jaw. It is possible to misdiagnose TMJ metastases as TMJ dysfunction or disorders. A patient’s history of a primary metastatic tumour may be a helpful guide in the search for secondary deposits and rule out the underlying malignancies of JB. In the present study, 62.2% of patients disclosed a prior history of primary BC, whereas 17.6% of patients did not disclose any prior BC.

JBM’s radiographic features are not pathognomonic. Osteolytic or osteoblastic lesions may result from a particular form of interaction between tumour cells and the bone microenvironment. The majority of cancers are identified by OL. Prostate cancer is a major cause of OB lesions.[58] Reactive new bone formation brought on by specific tumours can produce a lesion that is both radiolucent and radiopaque. In addition to interleukins IL-11, IL-8, and IL-6 and parathyroid hormone-related protein (PTHrP), which trigger osteoclast-mediated bone resorption by activating the RANK/RANKL/OPG signalling pathway, bioactive mediators are secreted by BC metastases that cause OL. The RANKL expression and L (OPG) expression of osteoblasts and other stromal cells are regulated by these mediators as a consequence of promoting osteoclast differentiation and activation, culminating in bone resorption.[59] 85% of lesions in the current study manifested as osteolytic with ill-defined radiolucency. In a few cases, radiographic interpretation was missing.

To assess the extent of soft tissue involvement and other sites of distant metastasis in the body, several modern imaging tools are necessary such as computerised tomography (CT) scans and magnetic resonance imaging (MRI) and Positron emission tomography (PET).

A biopsy is recommended for the histopathological examination to provide a conclusive diagnosis of the type of metastatic lesion. However, it might be difficult to make an exact diagnosis because of varied histological appearances, particularly when the major focus of the primary site is unknown. Histopathologically, BC has been divided into various subgroups. The World Health Organization’s classification 2022 has introduced many new entities in the BC.[70] There tends to be a histological preference for the site of distant metastasis; IDC of the breast tends to metastasize more commonly to the liver, lung, and brain compared to an ILC that tends to spread to bones, gynaecological and peritoneal organs.

For the histological analysis to provide a definitive diagnosis of the type of metastatic lesion, a biopsy is advised. However, due to the variable histological appearance, an accurate diagnosis may be challenging, especially if the primary focus is unknown. BC has been classified histopathologically into several subgroups. According to the World Health Organization’s classification, BC now includes a large number of additional entities.[70] The site of distant metastasis tends to have a histological predilection; for example, an IDC of the breast is more likely to spread to the brain, liver, and lung than an ILC, which is more likely to spread to the peritoneal, gynaecological, and bone organs. The reason for this has not been identified. In the current study, IDC and ILC were found to be the most predominant types of BC. Other tools, such as special staining, immunohistochemistry, and electron microscopy, may be necessary in some circumstances to determine the initial tumor’s nature. Imaging techniques such as Although BC entails multiorgan distant metastases, JB might occasionally be the only site of metastasis many times. 25.6% instances in this study had JB as the only location of RCC metastasis, whereas 32.4% had metastasis to other regions as well, such as lungs, vertebrae, spine, etc.

The treatment of choice for primary BC ranges from mastectomy to chemotherapy, radiotherapy, and hormonal therapy or even palliative treatment. Management for JBM includes a combination of surgical removal of solitary tumors, chemotherapy, radiotherapy, and endocrine therapy. The most commonly used therapeutic aids in this study were multiple therapies (27%). Other therapies used were chemotherapy, radiotherapy, and hormonal. Despite the proposed treatments, patients with metastatic involvement of JB have poor prognosis, with the 5-year survival rate reported to be 10%. According to the current study, only 20% of individuals died, with an average survival time of 1.8 years. 27% of patients had a good prognosis with no signs of recurrence. 4 cases are under follow-up.

Limitations of current research

One of the major limitations of our research was the lack of information provided for many parameters included for data extraction.

CONCLUSIONS

During the last 69 years (1954-2023), we found only 74 cases of BC metastasis to JB. This signifies a rare occurrence of JB metastasis from BC as the sole primary source. 20% of patients died, with a mean survival rate of 1.8 years. The mandible was the most affected jaw, followed by the Maxilla. Because they resemble primary neoplastic and non-neoplastic JB lesions, metastatic lesions go unnoticed the majority of the time. Their diagnosis is a challenging task for clinicians and pathologists. A thorough examination of the metastatic lesions is required, including a review of the patient’s medical history, clinical presentation, and early diagnosis to identify the primary site of metastasis and choose the best course of treatment.

Author’s contributions

• SG: Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources, Validation, Writing original draft, Writing review and editing.

• NA, AV, RV, MEMH, FM: Project administration, Supervision, Visualization.

Abbreviations used

BC: Breast cancer, CoCoPop: context, condition, population, CT: Computerized tomography GLOBACON: Global Cancer Observatory, IDC: Invasive ductal carcinoma, IL: Interleukins, ILC: Invasive lobular carcinoma, JB: Jaw bones, JBM: Jaw bone metastasis, LC: Lung cancer, MRI: Magnetic resonance imaging NA: Not available, OB: Osteoblastic, OL: Osteolytic, OST: Oral soft tissues, PET: Positron emission tomography, PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses, PTHrP: parathyroid hormone-related protein, STROBE: Strengthening the Reporting of Observational Studies in Epidemiology, TMJ: Temporomandibular joint.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.